Rearrangements of Chromosome Band 1p36 in Non-Hodgkin s Lymphoma 1
|
|
- Charlotte Barber
- 5 years ago
- Views:
Transcription
1 Vol. 5, , June 1999 Clinical Cancer Research 1401 Rearrangements of Chromosome Band 1p36 in Non-Hodgkin s Lymphoma 1 Bhavana J. Dave, Michelle M. Hess, Diane L. Pickering, Dianna H. Zaleski, Andrea L. Pfeifer, Dennis D. Weisenburger, James O. Armitage, and Warren G. Sanger 2 Human Genetics Laboratories, Munroe Meyer Institute for Genetics and Rehabilitation [B. J. D., M. M. H., D. L. P., D. H. Z., A. L. P., W. G. S.], and Departments of Pathology and Microbiology [D. D. W.] and Internal Medicine [J. O. A.], University of Nebraska Medical Center, Omaha, Nebraska ABSTRACT We studied 850 consecutive cases of histologically ascertained pretreatment non-hodgkin s lymphoma with cytogenetically abnormal clones. The diagnostic karyotypes revealed that 12% of these cases exhibited structural rearrangements involving chromosome band 1p36. Here, we describe the karyotypes of 53 cases containing a 1p36 rearrangement [often involving translocations of unknown material and presented as add(1)(p36)]. We used fluorescence in situ hybridization to determine the origin of the translocation partners. We report three different recurrent translocations involving 1p36. These include der(1)t(1;1)(p36; q21) (three cases), der(1)t(1;1)(p36;q25) (three cases), and der(1)t(1;9)(p36;q13) (four cases). Using cytogenetic and fluorescence in situ hybridization analyses, we have resolved the translocation partners in 31 cases. Rearrangements of band 1p36 were found among different histopathological subtypes. Alterations of 1p36 never occurred as a sole abnormality, and in 42 of 53 cases, alterations of the band 14q32 were observed. The t(14;18)(q32;q21) translocation was present in 35 cases. The significantly high occurrence of 1p36 breakpoint in structural rearrangements and its involvement in recurrent translocations suggest that the region is bearing gene(s) that are important in lymphomagenesis. Our study also showed that cytogenetically evident deletions were frequent in chromosome 1p, almost always Received 10/22/98; revised 3/4/99; accepted 3/16/99. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 1 Supported in part by grants from the Leukemia Society of America (Grant ), the Lymphoma Research Foundation of America, the National Cancer Institute (USPHS Grant CA36727), the Department of Health and Human Services, and the Cytogenetics Foundation at the University of Nebraska Medical Center-Munroe Meyer Institute. 2 To whom requests for reprints should be addressed, at Human Genetics Laboratories, Munroe Meyer Institute for Genetics and Rehabilitation, The University Nebraska Medical Center, , Nebraska Medical Center, Omaha, NE Phone: (402) ; Fax: (402) ; WGSANGER@UNMC.EDU. involving the p36 region, whereas duplications were rare and never encompassed the p36 region. Chromosome band 1p36 harbors many candidate tumor suppressor genes, and we propose that one or more of these genes might be deleted or functionally disrupted as a molecular consequence of the rearrangements, thus contributing to lymphomagenesis. INTRODUCTION NHLs 3 are a heterogeneous group of lymphoid neoplasms that display distinct morphological, immunological, cytogenetic, and molecular genetic features. Consistent structural chromosome aberrations in NHL have provided substantial insight into the genetic mechanisms of lymphomagenesis (1 4). The majority of NHL cases have clonal chromosome aberrations; however, tumors with sole karyotypic changes are relatively rare, constituting only 10 30% of the cases reported in large studies (5 7). Despite the complexity of the karyotypes, the recurrence of some karyotypic abnormalities in particular histopathological subtypes of NHL has been established. These include t(14;18) in follicular lymphomas, t(11;14) in mantle cell lymphomas, t(3;14) in diffuse large B-cell lymphomas, and t(8;14) in Burkitt s lymphoma (8 10). All of these rearrangements are balanced translocations, which involve the immunoglobulin heavy chain gene mapped to 14q32. The juxtaposition of different chromosomal loci, which bear oncogenes, to the actively transcribing immunoglobulin locus results in the activation of the proto-oncogenes and contributes to malignant transformation (11 13). The chromosomal translocations in NHL have, thus, been helpful in understanding oncogene activation via chromosomal rearrangement in neoplasia. In recent years, much attention has also been attracted to the role of tumor suppressor genes in malignant transformation. Deletion or loss of an entire chromosome or unbalanced structural rearrangements may lead to the inactivation or loss of a tumor suppressor gene(s). Independent lines of evidence suggest a role of the short arm of chromosome 1 in the suppression of biological parameters related to malignancy (14). Rearrangements of the distal segments of chromosome 1p are found in 10% of NHL cases (15, 16). However, because they are frequently reported to be in concert with other chromosomal changes, they are considered to be secondary abnormalities in NHL (17). Investigators have referred to a wide range of breakpoints between 1p32 36 (18 20). The purpose of this report was to focus on the involvement of chromosome band 1p36 in NHL and to determine the translocation partner chromosomes involved in the rearrangements with this chromosomal region. The data presented here are from a single institution-based study performed on pretreatment NHL cases. This 3 The abbreviations used are: NHL, non-hodgkin s lymphoma; FISH, fluorescence in situ hybridization.
2 1402 Rearrangements of Chromosome Band 1p36 in NHL Serial no. Case no. Source Table 1 Age (yr)/sex Pathology Clinical, histological, and cytogenetic characteristics of NHL cases a Cytogenetic nomenclature b LN c 48/M FSC 45,X, Y,add(1)(p36),t(2;8)(p12;q24),t(14;18)(q32;q21),add(18)(q23)[16]/46,XY[3] d LN 52/M FSC 47,XY,add(1)(p36), add(2)(p25), 7, 8,t(9;11)(q21;p11.2),t(14;18)(q32;q21)[17]/46,XY[3] LN 73/M FSC 46,XY,t(14;18)(q32;q21)[5]/46,idem, Y,t(1;9)(p36.1;p23), 11[2]/46,idem,der(6)t(6;15)(q11;q11.2), 12, 15[9]/45,X, Y[3]/46,XY[2] d LN 42/F FSC 47,XX,add(1)(p36),del(10)(q22q26),t(13;19)(q14;q13),t(14;18)(q32;q21), 16, 17, mar[cp18]/ 47,XX, X[2]/46,XX[1] d LN 47/M FM 49,XY,add(1)(p36),i(6)(p10),t(14;18)(q32;q21), der(18)t(14;18)(q32;q21) 2, mar[11]/46,xy[8] LN 45/M FM 49,XY,add(1)(p36), 7, 8,dup(12)(q13q23),t(14;18)(q32;q21), mar[16]/46,xy[4] LN 60/F FM 46,XX,del(7)(p13),t(14;18)(q32;q21)[3]/49,XX, X,add(1)(p36),t(14;18)(q32;q21), mar1, mar2[4] d LN 64/F FM 46,XX,add(1)(p36),dup(12)(q12q15),t(14;18)(q32;q21),der(17)t(1;17)(q21;p13)[18]/46,XX[2] d LN 36/M FM 48,XY,t(14;18)(q32;q21), mar1, mar2[9]/48,idem,add(1)(p36)[8] LN 28/F FM 48,XX,del(6)(q13q23),add(7)(p22),del(9)(q11q22),t(14;18)(q32;q21),add(16)(q24),i(17)(q10), 19, mar[9]/48,idem,der(1)add(1)(p36)del(1)(q11q32)[7]/46,xx[1] LN 61/F FM 47,XX, X,der(1)del(1)(q21q24)t(1;17)(p36;q21), 2, 7, 13, add(14)(q32),t(14;18)(q32;q21), 15, 17, der(18)t(14;18)(q32;q21), der(?)t(?;2)(?;q21)[16]/46,xx[4] LN 63/M FM 50,XY,der(1)t(1;1)(p36;q21),inv(1)(p36.1q21), 7, 8, 9,t(10;18)(q24;p11.3),t(14;18)(q32;q21), mar[10]/46,xy[10] LN 65/M FM 47,X,r(Y)(p11q12),del(1)(p36.1),i(6)(p10), 7,add(8)(p21),t(14;18)(q32;q21)[20] d LN 42/M FM 48,XY, X,t(14;18)(q32;q21), der(18)t(14;18)(q32;q21)[4]/48,idem,add(15)(q24)[2]/48,idem, add(3)(q26)[8]/48,idem,add(1)(p36),add(3)(q26)[2]/46,xy[4] LN 34/M FM 49,XY, X,t(1;6)(p36;q22),t(8;14)(q24;q13), 13, 19, 21, 22[3] LN 75/M FM 47,XY, i(x)(q10),t(1;11)(p36;q21),del(4)(q32),del(9)(q21),t(14;18)(q32;q21)[8]/46,xy[2] d LN 42/M FM 46,XY,der(1)add(1)(p36)dup(1)(q21q32),add(6)(q23),t(10;20)(q22;q21)[12]/47,idem, 2[4]/46,XY[5] LN 62/M FL-NC 47,XY,der(1)t(1;1)(p36;q25),der(8)t(X;8)(p11;p12),t(14;18)(q32;q21), mar[7]/47,idem,add(16) (q24)[2]/46,xy[10] LN 44/M FL-NC 49,XY,add(1)(p36), 8,t(14;18)(q32;q21), der(18)t(14;18)(q32;q21), mar[10]/46,xy[6] LN 42/F FL-NC 47,XX, X,add(1)(p36.1),t(14;18)(q32;q21)[7]/46,XX[3] LN 43/M FL-NC 47,XY,del(6)(q21), 8,t(14;18)(q32;q21),i(17)(q10)[1]/47,XY, 1, der(1)t(1;1)(p36;q11),del(6)(q21), 8,t(14;18)(q32;q21),i(17)(q10)[19] d LN 40/F FL-NC 48,XX,add(1)(p36), 3,add(6)(p25), 11,t(14;18)(q32;q21)[17]/46,XX[3] LN 58/M FL-NC 51,XY, Y,der(1)t(1;1)(p36;q21), 3,dup(12)(q13q15),t(14;18)(q32;q21), 18, der(18)t(14;18) (q32;q21), 21[16]/46,XY[4] LN 29/F FL-NC 46,XX,t(14;18)(q32;q21)[1]/53,XX,add(1)(p36),add(3)(q21),add(4)(q35),add(11)(p15),t(14;18) (q32;q21), 16, i(17)(q10), 18, 19, 20, mar1, mar2[26]/46,xx[1] LN 74/F FL-NC 47,X, X,add(1)(p36),t(3;10)(q26;q24), 4,i(6)(p10),der(7)t(1;7)(q22;q36),t(14;18)(q32;q21),del(15) (q22), 22, mar1, mar2[18]/46,xx[2] LN 58/M FL-NC 50,X, Y, X, del(1)(p22),der(1)add(1)(p36)del(1)(q21),del(6)(q14),del(7)(q22),add(12)(q22), t(14;18)(q32;q21), 16, 18, 20, mar[30]/46,xy[1] LN 77/M FL-NC 49,add(X)(p22.3),Y, add(x)(q28),t(1;6)(p36.3;p22), 5, 7,t(14;18)(q32;q21)[3]/46,XY[3] LN 82/M FL-NC 50,XY, X,add(1)(p36), 8, 12, 16[1]/100,idem 2[1] LN 59/F FL-NC 46,XX,t(1;14)(p36;q32),dup(3)(p21p25),add(10)(p15),add(22)(p12)[1]/47,XX,trp(3)(p21p25), 7, add(10)(p15),add(22)(p12)[11]/46,xx[7] d LN 76/F FL-NC 49,XX,add(1)(p36),t(2;6)(p25;q21), 9,r(13),t(14;18)(q32;q21),i(17)(q10), 19, 21[19]/46,XX[1] d LN 73/M FL-NC 47,XY,add(1)(p36), 7,t(14;18)(q32;q21)[21] ST 60/F FL-NC 47,X,add(X)(p22),add(1)(p36), 5,del(13)(q11q14),t(14;18)(q32;q21)[15]/46,XX[5] LN 79/F FL-NC 47,XX,t(1;14)(p36;q32),t(7;12)(q22;q24),add(17)(p13), 21[8]/46,XX[9] LN 65/F FL-NC 92,XXXX,add(1)(p36) 2,del(1)(q14q27),add(2)(p25) 2, 4, 4, 5,del(6)(q14q27),add(11)(q23) 2, add(16)(q13) 2,add(20)(p13), mar1, mar2, mar3[cp16]/46,xx[5] LN 49/M DSC 87,XXYY,add(1)(p36),del(1)(q22), 3, 4, 5, 6,add(8)(q24), 9, 11, 11,add(13)(q34) 2, add(14)(q32) 2, 15,i(17)(q10) 2, 20, mar1, mar2[1]/46,xy[1] LN 65/F DM-C/ NC 99,XXX,add(X)(p22),add(1)(p36), 6,del(6)(q21) 3, 12,dup(12)(q13q15) 2,add(14)(q32) 2, mar1, mar2, mar3, mar4, mar5[cp50] LN 59/M DL-NC 50,XY,del(1)(p12), der(1)add(1)(p36)del(1)(q12),del(3)(p24), 4,i(6)(p10), 8,del(10)(q22), 12, add(13)(q34),t(14;18)(q32;q21), 15,der(16)t(1;16)(q23;q13),add(17)(p13), mar1, mar2, mar3, mar4, mar5[cp13]/50,idem,add(19)(q13)[cp4]/46,xy[3] d,e LN 84/F DL-NC 47,XX,add(1)(p36),add(4)(q27),dup(12)(q13q24),dup(14)(q24q32),t(19;22)(q13.3;q11.2), mar[5]/46,xx[18] LN 54/M DL-NC 45,XY,t(1;18)(p36;p11), 8, 9,add(9)(p24),del(10)(q24),del(12)(p11), 16,add(19)(q13),add(20) (q13),add(21)(q22), mar1, mar2[11]/46,idem, Y,t(1;3;14)(q32;q23;q32), 2, 5, mar3, mar4[7]/48,idem,t(1;3;14)(q32;q23;q32), t(1;18)(p36;p11), t(1;18;?)(p36;p11;?), 2, add(13)(q34), mar3, mar4[3] LN 57/M DL-NC 46,X, Y,add(1)(p36),add(2)(p25),add(2)(q37), 5,hsr(12)(q14q21)[1]/48,idem, 6, 13,der(22) t(13;?;22)(q11;?;q13), mar1, mar2[19] LN 86/F DL-NC 49,X, X,der(1)add(1)(p36)del(1)(q25), der(2)t(1;2)(q21;q13), 3,der(4)t(4;10)(q21;q23), del(5)(q13q33), del(6)(q23), 7,t(9;10)(p11;p11), 17,add(18)(p11), add(19)(p13)[18]/46,xx[2]
3 Clinical Cancer Research 1403 Serial no. Case no. Source Age (yr)/sex Pathology Table 1 (Continued) Cytogenetic nomenclature b GIM 61/M DL-NC 45,X, X,der(1)t(1;1)(p36;q22),der(13)t(11;13)(q13;q33), 15,del(17)(p11), 21, mar1, mar2[20] LN 52/M DL-ML 48,XY,t(1;1)(p36;q25), 7, 12,t(14;18)(q32;q21)[20] f LN 25/M IBL 46,XY,add(1)(p36),add(5)(p15)[5]/92,idem 2[4]/46,XY[3] LN 68/M IBL 46,XY,t(1;16)(p36;q24),add(6)(p25),t(8;11)(q13;q23),der(17)t(1;17)(q12;p13)[18]/46,XY[2] LN 79/M IBL 79,XXY, X,der(1)t(1;1)(p36;q21), 2, 4,del(4)(q31), 7, 7, 7, 11,t(14;18)(q32;q21) 2, 15, 18, 18, 19,add(19)(p13) 2, 22, mar1, mar2[cp19]/46,xy[1] f LN 19/M IBL 88,XXYY, X, 1,add(1)(p36.3),t(1;3)(q21;p24), 2, der(3)t(1;3)(q21;p24), 4, 5, 5, 7, 8, del(10)(q22q24),del(10)(q22q25), 11,del(11)(q13),t(11;13)(q13;q32),der(13)t(11;13)(q13;q32), add(14)(q32), 17,i(17)(q10),add(18)(q11.2), 20,del(20)(q11.2) 2, mar[20] LN 66/F DL-NOS 90,XXXX,t(1;1)(p36;q25), 2, 3, 4,i(6)(p10),add(12)(q24),t(14;18)(q32;q21) 2, 20[11]/46,XX[7] SP 43/M NHL- NOS BM 32/F NHL- NOS BM 50/M NHL- NOS e LN 57/M NHL- NOS ST 43/M NHL- NOS 55,XY,der(1)t(1;1)(p36;q11),del(3)(p21),del(6)(q21), 7, 7,t(7;19)(q11;q13.3), 8, 8, add(13)(q34),t(14;18)(q32;q21),i(17)(q10), 19, 21, 22, mar[12]/95,idem 2, 2, 2, 4, 4, 13, 13, 15, 15, 20, 20[5]/46,XY[3] 46,XX,add(1)(p36),der(2)t(2;5)(p21;q31), 3,inv(3)(p22p25), 4,der(4)t(3;4;?)(p11.2;p16;?), der(5)t(5;7)(q11;p11),dup(5)(q15q31), 7,add(7)(q22), 8,add(11)(q23),del(13)(q22), add(13)(q34),t(14;18)(q32;q21), 16,i(17)(q10),add(19)(q13), 22, mar1, mar2[15]/94, idem 2, 2,del(3)(q21), 6, 10, 10, mar3, mar4, mar5 3, mar6[3]/46,xx[2] 52,XY,der(1)t(1;1)(p36;q23), 5, 7, 13,t(14;18)(q32;q21), 18, der(18)t(14;18)(q32;q21), mar[8]/46,xy[12] 76,XXY, add(1)(p32) 2,add(1)(p36), 2, 3,del(6)(q21), 10, 13, 14, 17, 20, 22, mar1, mar2, mar3,dmin[cp12]/46,xy[8] 47,XY,dic(1;1)(p36;p10),add(7)(p15),add(8)(p22),add(12)(p11), mar1[4]/48,idem,t(2;19)(p15;q13), mar2[3]/46,xy[13] a All cases were B-cell NHLs, unless otherwise indicated. b The nomenclature includes a single cell with the karyotype containing NHL specific abnormality and also a single cell with normal karyotype. c LN, lymph node; ST, soft tissue; T, tonsil; GIM, gastrointestinal mass; SP, spleen; BM, bone marrow; FSC, follicular small cleaved; FM, follicular mixed, small cleaved and large cell; FL-NC, follicular large cell noncleaved; DSC, diffuse small cleaved; DM-C/NC, diffuse mixed, small and large cell, cleaved and noncleaved; DL-NC, diffuse large cell noncleaved; DL-ML, diffuse large cell, multilobed; DL-NOS, diffuse large cell, not otherwise specified; IBL, immunoblastic; NHL-NOS, NHL, not otherwise specified. d Revised nomenclature (after FISH studies) is given in Table 3. e Immunologic characterization (T- or B-cell) not available. f Non-B-cell NHL. is the first report delineating the cases with pretreatment karyotypes exhibiting abnormalities of chromosome band 1p36, a region that includes many candidate tumor suppressor gene(s) (21 27). Because 1p36 alterations seldom occur as a sole abnormality and most often occur with other NHL-specific clonal abnormalities, these alterations are presumably a secondary change due to or leading to the disease. In an ongoing effort, we have used FISH to identify the origin of the translocation partner(s) on the derivative chromosome 1, and these data are included here. MATERIALS AND METHODS Patients/Specimens. Between January 1982 and December 1996, 1000 consecutive specimens (of which 850 contained abnormal karyotypes) were histologically confirmed as NHL at University of Nebraska Medical Center or other hospitals in Nebraska and western Iowa. The lymphomas have been classified according to the International Working Formulation (28). Biopsy materials were divided for histopathological, cytogenetic, and immunological analysis as described previously (29). B- or T-cell lineage has been assigned based on the results of immunophenotypic and/or immunogenotypic analysis. Cytogenetic studies in all these previously untreated cases have been performed following the protocol described previously (29). Cytogenetic Procedures. Briefly, chromosome preparations were obtained from lymph node biopsies according to conventional methods following 24-h short-term culture of mechanically disaggregated cells at 37 C in RPMI 1640 (Irvine Scientific, Santa Ana, CA) including 20% fetal bovine serum and antibiotics. The cultures were performed without the use of mitogens. One h before the initiation of harvest, the cells were exposed to colcemid (0.05 g/ml; Irvine Scientific). Following hypotonic treatment (0.074 M KCl solution for 20 min at 37 C), the cells were fixed in freshly prepared fixative, methanol: glacial acetic acid (3:1). After three washes with the fixative, air-dried slides were prepared and aged at 60 C overnight. Giemsa banding using Wright s stain (GW banding) was performed. When available, at least 20 metaphases were analyzed. Otherwise, as many metaphases as were available were characterized. Karyotypes were described according to International System for Human Cytogenetic Nomenclature, and those completed before 1995 have been revised according to the most recent nomenclature system (30). Chromosome abnormalities were defined as clonal if at least two cells had the same structural abnormality or gain of a chromosome or if three cells had loss of a specific chromosome. When an abnormal karyotype contained a known NHL-associated translocation [e.g., t(14; 18)(q32;q21)] and was observed in only one cell, we included it in the nomenclature. Also, even when a single normal karyotype was observed, it was included in the nomenclature. FISH Procedures. FISH was performed on fresh slides that were cytogenetically analyzed and/or in some cases slides
4 1404 Rearrangements of Chromosome Band 1p36 in NHL Fig. 2 Deletions and duplications of the regions in p arm of chromosome 1 among the NHL cases analyzed between 1982 and Fig. 1 Distribution of chromosome 1 breakpoints identified in histologically ascertained NHLs from 1982 to 1996., translocation; o, addition; and i, inversion. A single case with dicentric chromosome formation with breakpoint (p10) is not shown here. prepared from frozen fixed cell pellets, which have been maintained in our cell bank. Slides that were previously stained with GW staining procedures for cytogenetic analysis were destained by sequential washes in 70, 80, and 90% cold ethanol series for 10 min each. In cases for which fixed cell pellets were available, fresh slides were prepared using the cell suspension and aged following routine procedures for FISH (30 min in 2 SSC, ph 7.0, at 37 C). For each specimen, the selection of the probes to be used was dependent upon the most likely source of chromosome material as determined by cytogenetics. Commercially available chromosome painting probes, centromeric probes, cosmid probes, and satellite probes (Oncor, Inc., Gaithersburg, MD; and Vysis, Inc., Downers Grove, IL) were used for hybridization. Specific probes for centromeric regions of chromosome 1 were used to assist with target chromosome identification and chromosome-painting probes were used to identify the chromosome translocated to 1p36 region. Hybridization was performed following general protocols described for each specific probe used. Briefly, the slides were denatured in 70% formamide-2 SSC for 2 min at 72 C and then sequentially dehydrated. The probe mixture was denatured according to the manufacturer s protocol (Oncor or Vysis) before it was added to the target DNA and hybridized overnight. To circumvent the separate denaturation processes for the target DNA and the probes, we have also successfully used the Hybrite system (Vysis) for codenaturation using the program specified by the manufacturer for whole chromosome painting probes (WCP). Depending on the probes used (direct- or indirect-labeled), the postwashes and detection (in the case of indirect-labeled probes) were also carried out following the manufacturer s protocol. Following the hybridization and post wash process, the slides were counterstained with 4,6-diamino-2-phenylindol hydrochloride (DAPI; 0.1 g/ l). Analysis of the hybridization signals was performed on a Zeiss Axioscope equipped with appropriate filters and imaged with the Cytovision System for FISH and comparative genomic hybridization (Applied Imaging, Pittsburgh, PA). In the event of failure to determine the translocation partner chromosome with Table 2 Reciprocal breakpoints as partners of chromosome band 1p36, determined by cytogenetics and/or FISH Chromosome no. Reciprocal breakpoints of 1p36 1 p10, q11 (2 cases), q21 a (3 cases), q22, q23, q25 a (3 cases) 2 p13 3 q23 6 p22 (2 cases), q22 7 p21, q22 8 p22, q13 (2 cases) 9 p23, q13 a (4 cases) 11 q21 (2 cases) 14 q32 (2 cases) 16 q24 17 q21 18 p11 a Recurrent translocation breakpoints (i.e., observed in three or more cases). the specific probes used and when the available sample was small, slides were subjected to subsequent denaturation and hybridization with probes for other chromosomes. RESULTS Of the 850 pretreatment NHL, cytogenetically abnormal cases analyzed, 25% contained structural abnormalities of chromosome 1. Fifty % of these exhibited rearrangements involving band 1p36, including complete or partial deletions and duplications of 1p. Numerical anomalies of chromosome 1 were not considered in this analysis because no specific breakpoints are involved. Deletions and duplications result in the loss or amplification of a relatively large amount of genetic material encompassing a wide array of breakpoints. We have particularly focused only on those specimens with the karyotypic nomenclature precisely describing the rearrangement of 1p36. We observed that 1p36 rearrangements were significantly higher compared to other breakpoints on chromosome 1. Fig. 1 displays the relative frequency of the breakpoints involved in structural rearrangements of chromosome 1 in 213 cases. Duplications were very rare in the p arm of chromosome 1 and never involved the p36 region. However, deletions of 1p almost always involved the loss of 1p36 (Fig. 2). The karyotypes of the patients included in Fig. 2 are not described here, except for one
5 Clinical Cancer Research 1405 Table 3 Revised Cytogenetic Nomenclature of add(1)(p36) containing NHL cases after FISH studies Case no. Pathology Nomenclature FSC a 47,XY,add(1)(p36), add(2)(p25), 7, 8,t(9;11)(q21;p11.2),t(14;18)(q32;q21)[17]/46,XY[3].ish der(1)t(1;8)(p36;p22) (wcp8,d1z ) FSC 47,XX,add(1)(p36),del(10)(q22q26),t(13;19)(q14;q13),t(14;18)(q32;q21), 16, 17, mar[cp18]/47,xx, X[2]/46,XX[1].ish der(1)t(1;9)(p36;q13)(wcp9,d1z ) FM 49,XY,add(1)(p36),i(6)(p10),t(14;18)(q32;q21), der(18)t(14;18)(q32;q21) 2, mar[11]/46,xy[8].ish der(1)t(1;6) (p36;p22)(wcp6,d1z ) FM 46,XX,add(1)(p36),dup(12)(q12q15),t(14;18)(q32;q21),der(17)t(1;17)(q21;p13)[18]/46,XX[2].ish der(1)t(1;11)(p36;q21) (wcp11,d1z5 ) FM 48,XY,t(14;18)(q32;q21), mar1, mar2[9]/48,idem,add(1)(p36.3)[8].ish der(1)t(1;9)(p36;q13)(wcp9,d1z ) FM 48,XY, X,t(14;18)(q32;q21), der(18)t(14;18)(q32;q21)[4]/48,idem,add(15)(q24)[2]/48,idem,add(3)(q26)[8]/48,idem, add(1)(p36),add(3)(q26)[2]/46,xy[4].ish der(1)t(1;3)(p36;q23)(wcp3,d1z5 ) FM 46,XY,der(1)add(1)(p36)dup(1)(q21q32),add(6)(q23),t(10;20)(q22;q21)[12]/47,idem, 2[4]/46,XY[5].ish der(1)t(1;8)(p36;q13)dup(1)(q21q32)(wcp8,d1z ) FL-NC 48,XX,add(1)(p36), 3,add(6)(p25), 11,t(14;18)(q32;q21)[17]/46,XX[3].ish der(1)t(1;9)(p36;q13)(wcp9,d1z ) FL-NC 49,XX,add(1)(p36),t(2;6)(p25;q21), 9,r(13),t(14;18)(q32;q21),i(17)(q10), 19, 21[19]/46,XX[1].ish der(1)t(1;7) (p36;q22)(wcp7,d1z5 ) FL-NC 47,XY,add(1)(p36), 7,t(14;18)(q23;q21)[20].ish der(1)t(1;2)(p36;p13)(wcp2,d1z ) DL-NC 47,XX,add(1)(p36),add(4)(q27),dup(12)(q13q24),dup(14)(q24q32),t(19;22)(q13.3;q11.2), mar[5]/46,xx[18].ish der(1)t(1;9)(p36;q13)(wcp9,wcp1 ) a FSC, follicular small cleaved; FM, follicular mixed, small cleaved and large cell; FL-NC, follicular large cell noncleaved; DL-NC, diffuse large cell noncleaved. case, with a deletion of only the p36 region. (Table 1, serial no. 13). In both figures, we have described the number of specimens containing the abnormality; hence, any abnormality, even if it occurred more than once in the same karyotype, has been depicted only once in the figure. When two or more breakpoints were involved in one specimen, all of the breakpoints were noted (39 of 213 cases had more than one abnormality involving chromosome 1). The clinical characteristics, including age, sex, histological type of NHL, the source of specimens, and the complete karyotypes of the 53 NHL cases with 1p36 rearrangements, are described in Table 1. All cases were B-cell NHLs (except for two cases, indicated in Table 1). With an age range of years and a median age of 58 years, this group of patients included 35 males and 18 females. Specimens for cytogenetic analysis were collected from lymph node, bone marrow, spleen, tonsil, gastrointestinal mass, and soft tissue. Abnormalities of band 1p36 were found in low, intermediate, and high-grade NHLs. In 35 of 53 cases (66%), a 1p36 abnormality was present, together with t(14;18)(q32;q21). One specimen had a t(1;3; 14)(q32;q23;q32), and in two cases, there was a t(1;14)(p36; q32), involving the 14q32 region. Also, in four other cases (serial nos. 35, 36, 38, and 47), we found either a duplication or translocation of an unidentified chromosome involving band 14q32. Sixty % of the cases (32 of 53) containing 1p36 rearrangements were follicular lymphomas, 6% (3 of 53) were diffuse small cleaved or diffuse mixed lymphomas, and 23% (12 of 53) were diffuse lymphomas with large cell component or immunoblastic lymphomas. Fig. 3 depicts representative karyotypes of the abnormal clone containing a 1p36 abnormality from two cases. Table 2 describes the reciprocal breakpoints involved in translocation with 1p36. In 31 of 53 specimens, the translocation partners have been characterized, 11 of these were resolved by FISH. With clustering of breakpoints within 1q11 q25, chromosome 1 was the most frequent translocation partner (11 of 31 cases). In one case, a deletion of band 1p36 was observed. Also, a recurrent translocation involving chromosome band 9q13 was observed in four cases. In two cases, a t(1;14)(p36;q32) was observed. Table 3 presents the revised cytogenetic nomenclature for those cases in which FISH technique helped determine the translocation partners. Representative metaphases from the cases in which the FISH technique was used to determine the origin of unidentified segments translocated to 1p36 are shown in Fig. 4. DISCUSSION The incidence of NHL has been increasing during the past 15 years (31, 32). Much is known about the genetic changes occurring in different types of NHL, and yet much remains to be explored. There are many recurring cytogenetic abnormalities that have been associated with particular subtypes of lymphomas; however, the association has not been absolute, and new, cytogenetic, histological, and clinical correlations continue to be investigated. Large single-institution ascertainment of karyotypically abnormal cases continues to reveal novel clinical and histological subsets of lymphoid neoplasia, including NHL (15, 16, 18 20). These studies have also facilitated new molecular approaches to understand the etiology and clinical behavior of NHL. We have studied the diagnostic karyotypes of 850 NHL cases in which 12% of cases include a rearrangement of band 1p36. These chromosomal alterations include deletions, inversions, and balanced and unbalanced translocations. Recurrent chromosomal translocations have always served to facilitate the investigation of molecular changes and genes affected as a result of these translocations. Here, we describe three recurrent translocations involving chromosome band 1p36 (Tables 1 3). NHLs have shown one of the widest varieties of recurrent chromosomal changes, and these are not frequently seen as sole chromosomal alterations (33). In compiling recurrent abnormalities among hematological malignancies (includ-
6 1406 Rearrangements of Chromosome Band 1p36 in NHL Fig. 3 G-banded karyotypes of serial nos. 8 (A) and2(b; Table 1). Abnormal chromosomes from another metaphase spread from each of these cases are shown below the respective karyotypes. Photographs and revised nomenclature of these cases after FISH studies have been provided in Fig. 4, A and C, and Table 2. ing lymphomas), Mitelman et al. (33) described only those rearrangements that have been reported in three cases or more. Thirty cytogenetically different balanced recurrent abnormalities have been reported in NHL, and only one of these involved chromosome band 1p36, i.e. t(1;17)(p36;q21). This was reported in three cases, once as a sole abnormality. Also, 180 different recurrent unbalanced abnormal clones have been reported in NHL. These include defined unbalanced translocations resulting in duplications and/or deletions and derivative chromosomes. Only two unbalanced abnormalities
7 Clinical Cancer Research 1407 Fig. 4 Representative images of FISH analysis of serial nos. 8 (A),9(B),2(C), and 14 (D). A, red, wcp 11; green, D1Z5. B, red, wcp 9; green, D1Z. C, green, wcp 8; red, D1Z. D, red, wcp 3; green, D1Z5. Insets, G-banded chromosome 1 reported as add (1)(p36) by cytogenetic nomenclature prior to FISH studies and the translocation partner chromosomes. were related to band 1p36, i.e., del(1)(p36) and der(1)t(1; 1)(p36;q21). These were described in five cases each and never as a sole abnormality (33). Our data suggest that the translocation partners represent various chromosomes, with chromosome 1q11-q25 being the most frequent partner. We described three cases with der(1)t(1;1)(p36;q21) (Table 1, serial nos. 12, 23, and 46). Two other cases showed translocations of 1p36 with bands adjacent to q21, i.e., at q22 and q23, respectively (Table 1, serial nos. 42 and 51; Table 2). We also report another recurrent rearrangement of 1q25 with 1p36 (Table 1, serial nos. 18, 43, and 48). This occurred as a balanced translocation t(1;1)(p36;q25) in two cases and as a der(1)t(1;1)(p36;q25) in one case. All these cases also included a t(14;18)(q32;q21). This emphasizes that 1p36 rearrangements may be secondary alteration, due to or leading to NHL. The potential of FISH techniques to determine the origin of derivative and marker chromosomes and to improve the accuracy of cytogenetic interpretations is well accepted and is being applied as an adjunct to conventional cytogenetic analysis of many cancers, including lymphomas (34 37). There are two reports from a group of investigators (34, 35) describing the translocation partners of chromosome band 1p36 determined by FISH. The authors have resolved two and nine NHL cases, respectively; however, no recurrent translocation was reported. From our preliminary data, we are convinced that FISH analysis has helped in revealing the unknown material added to 1p36 and has helped define another recurrent translocation [der(1)t(1; 9)(p36;q13)] in NHL (Tables 1 3). Offit et al. (38) have shown that clusters of chromosome 9 aberrations involving 9q11 q13 were associated with diffuse lymphomas with a large cell component. However, the karyotypes described in their report did not have a reciprocal breakpoint on 1p36. The four cases showing the recurrent translocation t(1;9)(p36;q13) in our group of patients did not share a common histological subtype. We observed that duplications of chromosome 1p were very rare and never involved the p36 region, whereas deletions were frequent and almost always included p36 region as part of the deletion (Fig. 2). Chromosome rearrangements, like deletions, duplications, and translocations, may lead to amplifica-
8 1408 Rearrangements of Chromosome Band 1p36 in NHL tion, loss, or disruption of the functional ability of oncogenes and/or tumor suppressor genes located on that chromosomal region. In recent years, much attention has been directed to the role of tumor suppressor genes in malignant transformation (39, 40). Many candidate tumor suppressor genes have been mapped to chromosome 1p36. These include CDC2L1 (p58 or PITSLRE), a cell cycle-regulated kinase gene with homology to CDC2 (21, 22); TNFR2, one of the two tumor necrosis factor receptor genes (23); ID3, a member of the Id family of developmental negative regulatory genes (24); PAX7, the developmental regulator gene (25); and DAN, a transcription factor gene homologous to a mouse tumor suppressor gene (26). A very recent addition to this set of putative tumor suppressor genes on 1p36 is p73, a strong candidate suppressor gene that bears homology to p53 (27). Besides the cytogenetically visible deletions of chromosome 1p involving the p36 region, we hypothesize that as a molecular consequence of other structural rearrangements involving 1p36, one or more of the putative tumor suppressor gene(s) might be deleted or functionally disrupted. Loss of one or more of these candidate tumor suppressor genes on 1p36 have been extensively studied in neuroblastoma, in which deletion of 1p36 is considered a primary chromosomal change (41, 42). Deletions of tumor suppressor genes on 1p36 have also been investigated in many other cancers, including melanoma (43), intestinal cancer (44), and colon cancer (45), and more recently in ovarian cancer (46); however, there are no such reports on NHL. CDC2L1 is the most distally located candidate tumor suppressor gene on 1p36. Investigations to detect the possible deletion of this region are in progress in our laboratory, and we have observed the deletion of CDC2L1 gene locus among 23 of the 26 cases studied thus far (47). Whether the loss of this region containing putative tumor suppressor gene(s) significantly contributes to the disease progression and survival remains to be determined. It has been reported that the overall survival of the patients bearing breaks at 1p32 36 is shorter than that of the patients without these abnormalities (18). A correlation of breakpoints in this region suggested decreased disease-free survival (48). Breaks in this region, detected at the time of presentation or relapse, have also been correlated with bone marrow involvement in NHL (49). Clinical correlations of patients included in this study are in progress, and the data generated will provide insight into the probable role of 1p36 abnormalities in the survival of these patients. However, from the data compiled in this report, it is clearly evident that chromosome band 1p36 is implicated in NHL. REFERENCES 1. Yunis, J. J., Oken, M. M., Kaplan, M. E., Ensrud, K. M., Howe, R. B., and Theologides, A. Distinctive chromosomal abnormalities in histologic subtypes of non-hodgkin s lymphoma. N. Engl. J. Med., 307: , LeBeau, M. M. Chromosomal abnormalities in non-hodgkin s lymphomas. Semin. Oncol., 17: 20 29, Schouten, H., Sanger, W. G., and Armitage, J. O. Chromosomal abnormalities in malignant lymphoma and Hodgkin s disease. A review. Leuk. Lymphoma, 5: , Mrozek, K., and Bloomfield, C. D. Cytogenetics of non-hodgkin s lymphoma and Hodgkin s disease. In: P. H. Wiernik, G. P. Canellos, J. P. Dutcher, and R. A. Kyle (eds.), Neoplastic Diseases of Blood, Ed. 3, pp New York: Churchill Livingstone, Fifth International Workshop on Chromosomes in Leukemia-Lymphoma. Correlation of chromosome abnormalities with histologic and immunologic characteristics in non-hodgkin s lymphoma and adult T-cell leukemia-lymphoma. Blood, 70: , Levine, E. G., and Bloomfield, C. D. Cytogenetics of non-hodgkin s lymphoma. J. Natl. Cancer Inst. Monogr., 10: 7 12, Offit, K., and Chaganti, R. S. K. Chromosomal aberrations in non- Hodgkin s lymphoma. Biologic and clinical correlations. Hematol. Oncol. Clin. North Am., 5: , Mitelman, F. Catalog of Chromosome Aberrations in Cancer, Ed. 5. New York: Wiley-Liss, Rabbitts, T. H. Chromosomal translocations in human cancer. Nature (Lond.), 372: , Mrozek, K., and Bloomfield, C. D. New recurrent structural chromosome aberrations in non-hodgkin s lymphoma: a review of the published literature. Int. J. Oncol., 8: , Nowell, P. C., and Croce, C. M. Chromosome translocations and oncogenes in human lymphoid tumors. Am. J. Clin. Pathol., 94: , Dalla-Favera, R. Chromosomal translocations involving the c-myc oncogene in lymphoid neoplasia. In: I. R. Kirsch (ed.), The Causes and Consequences of Chromosomal Aberrations, pp Boca Raton, FL: CRC Press, Croce, C. M. Molecular biology of lymphomas. Semin. Oncol., 20: 31 46, Schwab, M., Cristian, P., and Amler, L. C. Genomic instability in 1p and human malignancies. Genes Chromosomes Cancer, 16: , Juneja, S., Lukeis, R., Tan, L., Cooper, I., Szelag, G., Parkin, J. D., Ironside, P., and Garson, O. M. Cytogenetic analysis of 147 cases of non-hodgkin s lymphoma: nonrandom chromosomal abnormalities and histological correlations. Br. J. Haematol., 76: , Hammond, D. W., Goepel, J. R., Aitken, M., Hancock, B. W., Potter, A. M., and Goyns, M. H. Cytogenetic analysis of a United Kingdom series of non-hodgkin s lymphomas. Cancer Genet. Cytogenet., 61: 31 38, Heim, S., and Mitelman, F. Cancer Cytogenetics. Chromosomal and Molecular Genetic Aberrations of Tumor Cells, pp New York: Alan R. Liss, Inc., Offit, K., Wong, G., Filippa, D. A., Tao, Y., and Chaganti, R. S. K. Cytogenetic analysis of 434 consecutively ascertained specimens of non-hodgkin s lymphoma: clinical correlations. Blood, 77: , Cabanillas, F., Pathak, S., Trujillo, J., Manning, J., Katz, R., McLaughlin, P., Velasquez, W. S., Hagemeister, F. B., Goodacre, A., Cork, A., Butler, J. J., and Freireich, E. J. Frequent nonrandom chromosome abnormalities in 27 patients with untreated large cell lymphoma and immunoblastic lymphoma. Cancer Res., 48: , Anderson, J. R., Vose, J. M., Bierman, P. J., Weisenburger, D. D., Sanger, W. G., Pierson, J., Bast, M., and Armitage, J. O. Clinical features and prognosis of follicular large-cell lymphoma: a report from the Nebraska Lymphoma Study Group. J. Clin. Oncol., 11: , Elipers, P. G., Barnoski, B. L., Han, J., Carroll, A. J., and Kidd, V. J. Localization of the expressed human p58 protein kinase chromosomal gene to chromosome 1p36 and a highly related sequence to chromosome 15. Genomics, 11: , Lahti, J. M., Valentine, M., Xiang, J., Jones, B., Amann, J., Grenet, J., Richmond, G., Look, A. T, and Kidd, V. J. Alterations in PITSLRE protein kinase gene complex on chromosome 1p36 in childhood neuroblastoma. Nat. Genet., 7: , White, P. S., Kaufman, B. A., Marshall, H. N., and Brodeur, G. M. Use of the single-strand conformation polymorphism technique to detect
9 Clinical Cancer Research 1409 loss of heterozygosity in neuroblastoma. Genes Chromosomes Cancer, 7: , Ellmeir, W., Aguzzi, A., Kleiner, E., Kurzbauer, R., and Weith, A. Mutually exclusive expression of a helix-loop-helix gene and N-myc in human neuroblastomas and in normal development. EMBO J., 11: , Shapiro, D. N., Sublett, J. E., Li, B., Valentine, M. B., Morris, S. W., and Noll, M. The gene for PAX7, a member of the paired-boxcontaining genes, is localized on human chromosome arm 1p36. Genomics, 17: , Enomoto, H., Ozaki, T., Takahashi, E., Nomura, N., Tabata, S., Takahashi, H., Ohnuma, N., Tanabe, M., Iwai, J., Yoshida, H., Matsunaga, T., and Sakiyama, S. Identification of human DAN gene mapping to the putative neuroblastoma tumor suppressor locus. Oncogene, 9: , Kaghad, M., Bonnet, H., Yang, A,. Creancier, L., Biscan, J. C., Valent, A., Minty, A., Chalon, P., Lelias, J. M., Dumont, X., Ferrara, P., Mckeeon, F., and Caput, D. Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other cancers. Cell, 90: , The Non-Hodgkin s Lymphoma Pathologic Classification Project. National Cancer Institute sponsored study of classification of non- Hodgkin s lymphomas: summary and description of a working formulation for clinical usage. Cancer (Phila.), 49: , Sanger, W. G., Armitage, J. O., Bridge, J. A., Weisenburger, D. D., Fordyce-Boyer, R., and Purtilo, D. T. Initial and subsequent cytogenetic studies in malignant lymphoma. Cancer (Phila.), 60: , Mitelman, F. (ed.). ISCN: An International System for Human Cytogenetic Nomenclature. Basel, Switzerland: S. Karger, Landis, S. H., Murray, T., Bolden, S., and Wingo, P. A. Cancer Statistics,. CA Cancer J. Clin., 48: 6 29, Skarin, A. T., and Dorfman, D. M. Non-Hodgkin s lymphomas. Current classification and management. CA Cancer J. Clin., 47: , Mitelman, F., Mertens, F., and Johansson, B. A breakpoint map of recurrent chromosomal rearrangements in human neoplasia. Nat. Genet., 15: , Bajalica, S., Sorensen, A., Pedersen, T., Heim, S., and Brondum- Nielsen, K. Chromosome painting as a supplement to cytogenetic banding analysis in non-hodgkin s lymphoma. Genes Chromosomes Cancer, 7: , Bajalica, S., Brondum-Nielsen, K., Sorensen, A., Pedersen, N. T., Kristoffersson, U., Akerman, M., Anderson, M., Pisa, P., and Nordenskjold, M. Characterization of add(1)(p36) in non-hodgkin Lymphomas by fluorescence in-situ hybridization. Genes Chromosomes Cancer, 13: 34 39, Hammond, D. W., Hancock, B. W., and Goyns, M. H. Analysis of 14q derivative chromosomes in non-hodgkin s lymphomas by fluorescence in-situ hybridization. Leuk. Lymphoma, 20: , Mathew, P., Sanger, W. G., Weisenburger, D. D., Valentine, M., Valentine, V., Pickering, D., Higgins, C., Hess, M., Cui, X., Srivastava, D. K., and Morris, S. W. Detection of the t(2;5)(p23;q35) and NPM- ALK fusion in Non-Hodgkin s lymphoma by two color fluorescence in situ hybridization. Blood, 89: , Offit, K., Parsa, N. Z., Jhanwar, S. C., Filippa, D., Wachtel, M., and Chaganti, R. S. K. Clusters of chromosome 9 aberrations are associated with clinico-pathologic subsets of non-hodgkin s lymphoma. Genes Chromosomes Cancer, 7: 1 7, Stanbridge, E. J. Functional evidence for human tumor suppressor genes: chromosome and molecular genetic studies. Cancer Surv., 12: 5 24, Knudson, A. G. Mutation and cancer: a personal odyssey. Adv. Cancer Res., 67: 1 23, Schwab, M., and Pearson, A. Genetics, cellular biology and clinical management of human neuroblastoma. Eur. J. Cancer, 31A: White, P. S., Maris, J. M., Beltinger, C., Sulman, E., Marshall, H. N., Fujimori, M., Kaufman, B. A., Beigel, J. A., Allen, C., Hilliard, C., Valentine, M. B., Look, A. T., Enomoto, H., Sakiyama, S., and Brodeur, G. M. A region of consistent deletion in neuroblastoma maps within human chromosome 1p Proc. Natl. Acad. Sci. USA, 92: , Dracopoli, N. C., Harnette, P., Bale, S. J., Stanger, B. Z., Tucker, M. A., Housman, D. E., and Kefford, R. F. Loss of alleles from the distal short arm of chromosome 1 occurs late in melanoma tumor progression. Proc. Natl. Acad. Sci. USA, 86: , Bardi, G., Pandis, C., Fenger, C., Kronborg, O., Bomme, L., and Heim, S. Deletion of 1p36 as a primary chromosomal aberration in intestinal tumorigenesis. Cancer Res., 53: , Tanaka, K., Yanoshita, R., Konishi, M., Oshimura, M., Maeda, Y., Mori, T., and Miyaki, M. Suppression of tumorigenicity in human colon carcinoma cells by introduction of normal chromosome 1p36 region. Oncogene, 8: , Thompson, F. H., Taetle, R., Trent, J. M., Liu, Y., Massey-Brown, K., Scott, K. M., Weinstein, R. S., Emerson, J. C., Alberts, D. S., and Nelson, M. A. Band 1p36 abnormalities and t(1;17) in ovarian carcinoma. Cancer Genet. Cytogenet., 96: , Dave, B. J., Pickering, D. L., Hess, M. M., Weisenburger, D. D., Armitage, J. O., and Sanger, W. G. Deletion of Cell Division Cycle 2 Like 1 gene locus on chromosome 1p36 in non-hodgkin s lymphoma. Cancer Genet. Cytogenet., 108: , Levine, E. G., Arthur, D. C., Frizzera, G., Peterson, B. A., Hurd, D. A., and Bloomfield, C. D. Cytogenetic abnormalities predict clinical outcome in non-hodgkin s lymphoma. Ann. Intern. Med., 108: 14 20, Offit, K., Richardson, M., Chen, Q., Hampton, A., Koduru, P., Jhanwar, S., Filippa, D., Leiberman, P., Clarkson, B. D., and Chaganti, R. S. K. Nonrandom chromosomal aberrations are associated with sites of tissue involvement in non-hodgkin s lymphoma. Cancer Genet. Cytogenet., 37: 85 93, 1989.
10 Rearrangements of Chromosome Band 1p36 in Non-Hodgkin's Lymphoma Bhavana J. Dave, Michelle M. Hess, Diane L. Pickering, et al. Clin Cancer Res 1999;5: Updated version Access the most recent version of this article at: Cited articles Citing articles This article cites 39 articles, 8 of which you can access for free at: This article has been cited by 3 HighWire-hosted articles. Access the articles at: alerts Sign up to receive free -alerts related to this article or journal. Reprints and Subscriptions Permissions To order reprints of this article or to subscribe to the journal, contact the AACR Publications Department at pubs@aacr.org. To request permission to re-use all or part of this article, use this link Click on "Request Permissions" which will take you to the Copyright Clearance Center's (CCC) Rightslink site.
Role of FISH in Hematological Cancers
Role of FISH in Hematological Cancers Thomas S.K. Wan PhD,FRCPath,FFSc(RCPA) Honorary Professor, Department of Pathology & Clinical Biochemistry, Queen Mary Hospital, University of Hong Kong. e-mail: wantsk@hku.hk
More informationReporting cytogenetics Can it make sense? Daniel Weisdorf MD University of Minnesota
Reporting cytogenetics Can it make sense? Daniel Weisdorf MD University of Minnesota Reporting cytogenetics What is it? Terminology Clinical value What details are important Diagnostic Tools for Leukemia
More informationCYTOGENETICS Dr. Mary Ann Perle
CYTOGENETICS Dr. Mary Ann Perle I) Mitosis and metaphase chromosomes A) Chromosomes are most fully condensed and clearly distinguishable during mitosis. B) Mitosis (M phase) takes 1 to 2 hrs and is divided
More informationCytogenetic Findings in Mantle Cell Lymphoma Cases With a High Level of Peripheral Blood Involvement Have a Distinct Pattern of Abnormalities
Hematopathology / MANTLE CELL LYMPHOMA Cytogenetic Findings in Mantle Cell Lymphoma Cases With a High Level of Peripheral Blood Involvement Have a Distinct Pattern of Abnormalities Mihaela Onciu, MD, 1*
More informationChromosomal Aberrations
Chromosomal Aberrations Chromosomal Aberrations Abnormalities of chromosomes may be either numerical or structural and may involve one or more autosomes, sex chromosomes, or both simultaneously. Numerical
More informationSignificance of Chromosome Changes in Hematological Disorders and Solid Tumors
Significance of Chromosome Changes in Hematological Disorders and Solid Tumors Size of Components of Human Genome Size of haploid genome 3.3 X 10 9 DNA basepairs Estimated genetic constitution 30,000
More informationSignificance of Chromosome Changes in Hematological Disorders and Solid Tumors
Significance of Chromosome Changes in Hematological Disorders and Solid Tumors Size of Components of Human Genome Size of haploid genome! Estimated genetic constitution! Size of average chromosome
More informationHaematology Probes for Multiple Myeloma
Haematology Probes for Multiple Myeloma MULTIPLE MYELOMA Multiple myeloma (MM) is a plasma cell neoplasm, characterised by the accumulation of clonal plasma cells in the bone marrow and by very complex
More informationJames R. Cook, MD, PhD, 1 Sofia Shekhter-Levin, PhD, 2 and Steven H. Swerdlow, MD 3. Abstract
Hematopathology / ROUTINE CYTOGENETICS FOR SUSPECTED LYMPHOMA Utility of Routine Classical Cytogenetic Studies in the Evaluation of Suspected Lymphomas Results of 279 Consecutive Lymph Node/Extranodal
More informationAn International System for Human Cytogenetic Nomenclature (2013)
ISCN 2013 An International System for Human Cytogenetic Nomenclature (2013) Editors Lisa G. Shaffer Jean McGowan-Jordan Michael Schmid Recommendations of the International Standing Committee on Human Cytogenetic
More informationOncology Genetics: Cytogenetics and FISH 17/09/2014
Oncology Genetics: Cytogenetics and FISH 17/09/2014 Chris Wragg Head of Oncology Genomics, BGL BGL Bristol Genetics Laboratory (BGL) CPA accredited Genetics laboratory serving a core population of 4-5million
More informationACUTE LYMPHOBLASTIC leukemia (ALL) affecting T
NEOPLASIA Spectral Karyotype Analysis of T-Cell Acute Leukemia By Janet D. Rowley, Shalini Reshmi, Katrin Carlson, and Diane Roulston Analysis of 15 cases of T-cell acute lymphoblastic leukemia with spectral
More informationGENETIC MARKERS IN LYMPHOMA a practical overview. P. Heimann Dpt of Medical Genetics Erasme Hospital - Bordet Institute
GENETIC MARKERS IN LYMPHOMA a practical overview P. Heimann Dpt of Medical Genetics Erasme Hospital - Bordet Institute B and T cell monoclonalities Rearrangement of immunoglobin and TCR genes may help
More informationCYTOGENETIC STUDY OF 50 DE NOVO CASES OF ANLL FROM ARGENTINA. Susana Acevedo, Irma Slavutsky, Gabriela Andreoli, Irene Larripa
original paper Haematologica 1994; 79:40-5 CYTOGENETIC STUDY OF 50 DE NOVO CASES OF ANLL FROM ARGENTINA Susana Acevedo, Irma Slavutsky, Gabriela Andreoli, Irene Larripa Departamento de Genética, División
More informationFluorescent in situ hybridization studies in multiple myeloma
Fluorescent in situ hybridization studies in multiple myeloma Ozge Ozalp Yuregir 1, Feride Iffet Sahin 1, Zerrin Yilmaz 1, Ebru Kizilkilic 2, Sema Karakus 2 and Hakan Ozdogu 2 1 Department of Medical Genetics
More informationBHS training course. Laboratory Hematology Cytogenetics. Lucienne Michaux. Centrum voor Menselijke Erfelijkheid, UZLeuven
BHS training course Laboratory Hematology Cytogenetics Lucienne Michaux Centrum voor Menselijke Erfelijkheid, UZLeuven 18/11/2017 Organization of the Lecture Definition and principles Tools Applications
More informationO steosarcoma is the most common primary bone
389 SHORT REPORT Evaluation of paediatric osteosarcomas by classic cytogenetic and CGH analyses J R Batanian, L R Cavalli, N M Aldosari, E Ma, C Sotelo-Avila, M B Ramos, J D Rone, C M Thorpe, B R Haddad...
More informationUse of MYC, BCL2 and BCL6 FISH for investigations of high grade B cell lymphoma
Use of MYC, BCL2 and BCL6 FISH for investigations of high grade B cell lymphoma Dr Anthony Bench Haematopathology and Oncology Diagnostic Service Cambrıdge Unıversıty Hospitals NHS Foundatıon Trust Cambridge
More informationSection E of the ACMG technical standards and guidelines: chromosome studies of lymph node and solid tumor acquired chromosomal abnormalities
American College of Medical Genetics and Genomics ACMG Standards and Guidelines Section E6.5 6.8 of the ACMG technical standards and guidelines: chromosome studies of lymph node and solid tumor acquired
More informationt(14;18), affecting bcl-2, and 3q27 rearrangement,
NEOPLASIA Follicular lymphoma grade 3B includes 3 cytogenetically defined subgroups with primary t(14;18), 3q27, or other translocations: t(14;18) and 3q27 are mutually exclusive Anneke G. Bosga-Bouwer,
More informationCLL Complete SM Report
Reported: 02/01/2012 Σ CGI ID No:5 Client:r Client Address: CLINICAL DATA: Lymphoma No CBC results provided. CLL Complete SM Report FINAL DIAGNOSIS: CD19+ B cell lymphoma, ZAP-70 + (44%), with borderline
More informationCCND1-IGH Fusion-Amplification and MYC Copy Number Gain in a Case of Pleomorphic Variant Mantle Cell Lymphoma
AJCP /CASE REPORT CCND1-IGH Fusion-Amplification and MYC Copy Number Gain in a Case of Pleomorphic Variant Mantle Cell Lymphoma Yuan Miao, MD, 1,2 Pei Lin, MD, 1 Wei Wang, MD, 1 L. Jeffrey Medeiros, MD,
More informationActivation of cellular proto-oncogenes to oncogenes. How was active Ras identified?
Dominant Acting Oncogenes Eugene E. Marcantonio, M.D. Ph.D. Oncogenes are altered forms of normal cellular genes called proto-oncogenes that are involved in pathways regulating cell growth, differentiation,
More informationCanadian College of Medical Geneticists (CCMG) Cytogenetics Examination. May 4, 2010
Canadian College of Medical Geneticists (CCMG) Cytogenetics Examination May 4, 2010 Examination Length = 3 hours Total Marks = 100 (7 questions) Total Pages = 8 (including cover sheet and 2 pages of prints)
More informationCytogenetic and CGH studies in a case of pulmonary hamartoma
Turkish Journal of Cancer Vol.31/ No. 1/2001 Cytogenetic and CGH studies in a case of pulmonary hamartoma SİBEL BERKER KARAÜZÜM 1, İBRAHİM KESER 1, GÜVEN LÜLECİ 1, NADİR PAKSOY 2, ABİD DEMİRCAN 3 Departments
More informationTemplate for Reporting Results of Monitoring Tests for Patients With Chronic Myelogenous Leukemia (BCR-ABL1+)
Template for Reporting Results of Monitoring Tests for Patients With Chronic Myelogenous Leukemia (BCR-ABL1+) Version: CMLBiomarkers 1.0.0.2 Protocol Posting Date: June 2017 This biomarker template is
More informationACMG/CAP Cytogenetics CY
www.cap.org Cytogenetics Analytes/procedures in bold type are regulated for proficiency testing by the Centers for Medicare & Medicaid Services ACMG/CAP Cytogenetics CY Analyte CY Challenges per Shipment
More informationUnderstanding the Human Karyotype Colleen Jackson Cook, Ph.D.
Understanding the Human Karyotype Colleen Jackson Cook, Ph.D. SUPPLEMENTAL READING Nussbaum, RL, McInnes, RR, and Willard HF (2007) Thompson and Thompson Genetics in Medicine, 7th edition. Saunders: Philadelphia.
More informationCost-Effective Strategies in the Workup of Hematologic Neoplasm. Karl S. Theil, Claudiu V. Cotta Cleveland Clinic
Cost-Effective Strategies in the Workup of Hematologic Neoplasm Karl S. Theil, Claudiu V. Cotta Cleveland Clinic In the past 12 months, we have not had a significant financial interest or other relationship
More informationESMO DOUBLE-HIT LYMPHOMAS
ESMO DOUBLE-HIT LYMPHOMAS Professor Dr. med. Georg Lenz Director Department of Hematology and Oncology Universitätsklinikum Münster, Germany OVERVIEW Definition of double-hit lymphomas Introduction in
More informationMitelman Database of Chromosome Aberrations and Gene Fusions in Cancer
Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer (2017). Mitelman F, Johansson B and Mertens F (Eds.), http://cgap.nci.nih.gov/chromosomes/mitel
More informationFluorescence in-situ Hybridization (FISH) ETO(RUNX1T1)/AML1(RUNX1) or t(8;21)(q21.3;q22)
PML/RARA t(15;17) Translocation Assay Result : nuc ish(pml 2)(RARA 2)[200] : 200/200(100%) interphase nuclei show normal 2O 2G signals for PML/RARA : is Negative for t(15;17)(q22;q21.1) 2 Orange 2 Green
More informationNucleic Acid Testing - Oncology. Molecular Diagnosis. Gain/Loss of Nucleic Acid. Objectives. MYCN and Neuroblastoma. Molecular Diagnosis
Nucleic Acid Testing - Oncology Molecular Diagnosis Nucleic acid based testing in Oncology Gross alterations in DNA content of tumors (ploidy) Gain/Loss of nucleic acids Markers of Clonality Oncogene/Tumor
More informationMolecular Diagnosis. Nucleic acid based testing in Oncology
Molecular Diagnosis Nucleic acid based testing in Oncology Objectives Describe uses of NAT in Oncology Diagnosis, Prediction, monitoring. Genetics Screening, presymptomatic testing, diagnostic testing,
More informationVolume 7, Issue 1 January 2012
The Hong Kong College of Pathologists, Incorporated in Hong Kong with Limited Liability Volume 7, Issue 1 January 2012 Editorial note: Chronic lymphocytic leukaemia (CLL) is the commonest chronic lymphoproliferative
More informationHematopathology Service Memorial Sloan Kettering Cancer Center, New York
SH2017-0334 t(14;18) Negative Follicular Lymphoma with 1p36 abnormality associated with In Situ Follicular Neoplasia with t(14;18) translocation Pallavi Khattar MD, Jennifer Maerki MD, Alexander Chan MD,
More informationP53 Gene Deletion Detected By Fluorescence In Situ Hybridization is an Adverse
Blood First Edition Paper, prepublished online August 31, 2004; DOI 10.1182/blood-2004-04-1363 P53 Gene Deletion Detected By Fluorescence In Situ Hybridization is an Adverse Prognostic Factor for Patients
More informationStructural Variation and Medical Genomics
Structural Variation and Medical Genomics Andrew King Department of Biomedical Informatics July 8, 2014 You already know about small scale genetic mutations Single nucleotide polymorphism (SNPs) Deletions,
More informationKey words: chromosomes, breast cancer, chromosome microdissection, physical mapping
Breast Cancer Research and Treatment 33: 95-102, 1995. 1995 Kluwer Academic Publishers. Printed in the Netherlands. Molecular Genetics in Breast Cancer- minisymposium Mierodisseetion and mieroeloning of
More informationFluorescent In-Situ Hybridization is the Hand Mirror of Cytogenetics: A Rare Case of Near Tetraploidy in Pediatric Acute Lymphoblastic Leukemia
American Journal of Cancer Case Reports Rajan A et al. American Journal of Cancer Case Reports 2016, 4:156-160 http://ivyunion.org/index.php/ajccr/ Page 1 of 5 Case Report Fluorescent In-Situ Hybridization
More informationChapter 4 Cellular Oncogenes ~ 4.6 -
Chapter 4 Cellular Oncogenes - 4.2 ~ 4.6 - Many retroviruses carrying oncogenes have been found in chickens and mice However, attempts undertaken during the 1970s to isolate viruses from most types of
More informationClassification of Hematologic Malignancies. Patricia Aoun MD MPH
Classification of Hematologic Malignancies Patricia Aoun MD MPH Objectives Know the basic principles of the current classification system for hematopoietic and lymphoid malignancies Understand the differences
More informationCancer cytogenetics update 2005
Atlas of Genetics and Cytogenetics in Oncology and Haematology Cancer cytogenetics update 2005 Felix Mitelman Department of Clinical Genetics, University of Lund, Lund, Sweden March 2005 By January 2005,
More informationAggressive B-cell Lymphomas Updated WHO classification Elias Campo
Aggressive B-cell Lymphomas Updated WHO classification Elias Campo Hospital Clinic, University of Barcelona Diffuse Large B-cell Lymphoma A Heterogeneous Category Subtypes with differing: Histology and
More informationFISH VALIDATION: HOW I DO IT!
FISH VALIDATION: HOW I DO IT! Theresa C. Brown, PhD, FACMG, CG(ASCP) CM Director, Cytogenetics laboratory Hayward Genetics Center Instructor Tulane University School of Medicine WHERE DO I GET THIS INFORMATION
More informationDetection of abl/bcr Fusion Gene in Patients Affected by Chronic Myeloid Leukaemia by Dual-Colour Interphase Fluorescence in situ Hybridisation
Journal of Sciences, Islamic Republic of Iran 15(4): 321-325 (2004) University of Tehran, ISSN 1016-1104 Detection of abl/bcr Fusion Gene in Patients Affected by Chronic Myeloid Leukaemia by Dual-Colour
More informationImmunopathology of Lymphoma
Immunopathology of Lymphoma Noraidah Masir MBBCh, M.Med (Pathology), D.Phil. Department of Pathology Faculty of Medicine Universiti Kebangsaan Malaysia Lymphoma classification has been challenging to pathologists.
More informationTemplate for Reporting Results of Biomarker Testing of Specimens From Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Template for Reporting Results of Biomarker Testing of Specimens From Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Version: CLLBiomarkers 1.0.0.2 Protocol Posting Date: June 2017
More informationTest Name Results Units Bio. Ref. Interval. Positive
LL - LL-ROHINI (NATIONAL REFERENCE 135091533 Age 28 Years Gender Male 1/9/2017 120000AM 1/9/2017 105415AM 4/9/2017 23858M Ref By Final LEUKEMIA DIAGNOSTIC COMREHENSIVE ROFILE, ANY 6 MARKERS t (1;19) (q23
More informationUveal melanoma (UM) is the most common primary intraocular
A R T I C L E S Clinical and Cytogenetic Analyses in Uveal Melanoma Emine Kilic, 1 Walter van Gils, 1,2 Elisabeth Lodder, 2 H. Berna Beverloo, 2 Marjan E. van Til, 2 Cornelia M. Mooy, 3 Dion Paridaens,
More informationMethods used to diagnose lymphomas
Institut für Pathologie Institut für Pathologie Methods used to diagnose lymphomas Prof. Dr.Med. Leticia Quintanilla-Fend Molecular techniques NGS histology Cytology AS-PCR Sanger seq. MYC Immunohistochemistry
More informationSplenic marginal zone B-cell lymphoma (SMZBCL) is
Malignant Lymphomas Splenic marginal zone B-cell lymphomas: two cytogenetic subtypes, one with gain of 3q and the other with loss of 7q Design and Methods Patients Forty-seven patients with a diagnosis
More informationDetermination of Genomic Imbalances by Genome-wide Screening Approaches
Overview Determination of Genomic Imbalances by Genome-wide Screening Approaches Károly Szuhai Introduction/Methodologies Applications/Results Conclusion Approaches Introduction/Methodologies Chromosome
More informationDetection of Anaplastic Lymphoma Kinase (ALK) gene in Non-Small Cell lung Cancer (NSCLC) By CISH Technique
Cancer and Clinical Oncology; Vol. 7, No. 1; 2018 ISSN 1927-4858 E-ISSN 1927-4866 Published by Canadian Center of Science and Education Detection of Anaplastic Lymphoma Kinase (ALK) gene in Non-Small Cell
More informationCancer Cytogenetics: Chromosomal And Molecular Genetic Abberations Of Tumor Cells By Sverre Heim READ ONLINE
Cancer Cytogenetics: Chromosomal And Molecular Genetic Abberations Of Tumor Cells By Sverre Heim READ ONLINE If you are looking for the ebook by Sverre Heim Cancer Cytogenetics: Chromosomal and Molecular
More informationCase Report A case of EBV positive diffuse large B-cell lymphoma of the adolescent
Int J Clin Exp Med 2014;7(1):307-311 www.ijcem.com /ISSN:1940-5901/IJCEM1311029 Case Report A case of EBV positive diffuse large B-cell lymphoma of the adolescent Qilin Ao 2, Ying Wang 1, Sanpeng Xu 2,
More informationTITLE: Identification of Chromosomes Alterations in Primary Breast Cancer Using Premature Chromosome Condensation
AD Award Number: DAMD17-99-1-9237 TITLE: Identification of Chromosomes Alterations in Primary Breast Cancer Using Premature Chromosome Condensation PRINCIPAL INVESTIGATOR: Constance A. Griffin, M.D. CONTRACTING
More informationPhenoPath. Diagnoses you can count on B CELL NON-HODGKIN LYMPHOMA
PhenoPath Diagnoses you can count on B CELL NON-HODGKIN LYMPHOMA C urrent diagnosis of B cell non-hodgkin lymphoma (B-NHL) is based on the 2008 WHO Classification of Tumours of Haematopoietic and Lymphoid
More informationVariations in Chromosome Structure & Function. Ch. 8
Variations in Chromosome Structure & Function Ch. 8 1 INTRODUCTION! Genetic variation refers to differences between members of the same species or those of different species Allelic variations are due
More informationCase 3. Ann T. Moriarty,MD
Case 3 Ann T. Moriarty,MD Case 3 59 year old male with asymptomatic cervical lymphadenopathy. These images are from a fine needle biopsy of a left cervical lymph node. Image 1 Papanicolaou Stained smear,100x.
More informationAcute Promyelocytic Leukemia with i(17)(q10)
CASE REPORT Acute Promyelocytic Leukemia with i(17)(q10) Junki Inamura 1, Katsuya Ikuta 2, Nodoka Tsukada 1, Takaaki Hosoki 1, Motohiro Shindo 2 and Kazuya Sato 1 Abstract We herein report a rare chromosomal
More informationOutline. Chromosomal analysis FISH. Chromosomal abnormalities in cancer. Clinical application of cytogenetics. Procedure Nomenclature
Outline Chromosomal analysis Procedure Nomenclature FISH Procedure Probes Multicolor-FISH CGH Chromosomal abnormalities in cancer CML, MPD, MDS, AML, ALL, CLL, myeloma, lymphoma Clinical application of
More informationAddressing the challenges of genomic characterization of hematologic malignancies using microarrays
Addressing the challenges of genomic characterization of hematologic malignancies using microarrays Sarah South, PhD, FACMG Medical Director, ARUP Laboratories Department of Pediatrics and Pathology University
More informationCytogenetic analyses in malignant hematological disorders
Cytogenetic analyses in malignant hematological disorders general concepts Lucienne Michaux Lessenreeks 21/11/2017 Plan Definition History Pathophysiology of malignant hematological disorders Techniques
More informationChromosome aberrations in a series of 120 multiple myeloma cases with abnormal karyotypes
Chromosome aberrations in a series of 120 multiple myeloma cases with abnormal karyotypes Anwar N. Mohamed, 1,2 * Gail Bentley, 1 Michelle L. Bonnett, 1 Jeff Zonder, 3 and Ayad Al-Katib 3 1 Department
More informationDefined lymphoma entities in the current WHO classification
Defined lymphoma entities in the current WHO classification Luca Mazzucchelli Istituto cantonale di patologia, Locarno Bellinzona, January 29-31, 2016 Evolution of lymphoma classification Rappaport Lukes
More informationChromosome pathology
Chromosome pathology S. Dahoun Department of Gynecology and Obstetrics, University Hospital of Geneva Cytogenetics is the study of chromosomes and the related disease states caused by abnormal chromosome
More informationGenetic Stability of Autologous Human Smooth Muscle Cells
Genetic Stability of Autologous Human Smooth Muscle Cells TERMIS-NA, Houston, TX, December 11-14, 2011 D.M. Justewicz*, T.B. Burnette, J.E. Shokes, T. Spencer, D. Jain * Corresponding Author 1 Study Objective
More informationPathology of the indolent B-cell lymphomas Elias Campo
Pathology of the indolent B-cell lymphomas Elias Campo Hospital Clinic, University of Barcelona Small B-cell lymphomas Antigen selection NAIVE -B LYMPHOCYTE MEMORY B-CELL MCL FL LPL MZL CLL Small cell
More informationThe next lymphoma classification Luca Mazzucchelli Istituto cantonale di patologia, Locarno
Evolution of classification The next classification Luca Mazzucchelli Istituto cantonale di patologia, Locarno The Lymphoma Forum of Excellence, Bellinzona, January 2011 Rappaport Lukes and Collins (immunophenotype)
More informationGenomic complexity and arrays in CLL. Gian Matteo Rigolin, MD, PhD St. Anna University Hospital Ferrara, Italy
Genomic complexity and arrays in CLL Gian Matteo Rigolin, MD, PhD St. Anna University Hospital Ferrara, Italy Clinical relevance of genomic complexity (GC) in CLL GC has been identified as a critical negative
More informationAbstract. Hematopathology / Improved Cytogenetics in Lymphoma. Key Words: Cytogenetics; B-cell lymphoma; CpG-oligonucleotide DSP30
Hematopathology / Improved Cytogenetics in Lymphoma Improved Detection Rate of Cytogenetic Abnormalities in Chronic Lymphocytic Leukemia and Other Mature B-Cell Neoplasms With Use of CpG-Oligonucleotide
More informationChromosome Abnormalities
Chromosome Abnormalities Chromosomal abnormalities vs. molecular mutations Simply a matter of size Chromosomal abnormalities are big errors Two types of abnormalities 1. Constitutional problem present
More informationDo acgh analysis have a place in routine cytogenetic workup in leukemia/cancer? - A single institution experience. Cambridge, April 9 th 2013
Do acgh analysis have a place in routine cytogenetic workup in leukemia/cancer? - A single institution experience. Cambridge, April 9 th 2013 Aarhus University Hospital Eigil Kjeldsen, Cancercytogenetic
More informationChapter 3 Chromosomal Aberrations
MEDICAL GENETICS Chapter 3 Chromosomal Aberrations Abnormalities of chromosomes may be either numerical or structural and may involve one or more autosomes, sex chromosomes, or both simultaneously. Numerical
More informationIntegration of microarray analysis into the clinical diagnosis of hematological malignancies: How much can we improve cytogenetic testing?
/, Vol. 6, No. 22 Integration of microarray analysis into the clinical diagnosis of hematological malignancies: How much can we improve cytogenetic testing? Jess F. Peterson 1,2,6, Nidhi Aggarwal 3, Clayton
More informationIntronic BCL-6 mutations are preferentially targeted to the translocated allele in t(3;14)(q27;q32) non-hodgkin B-cell lymphoma
NEOPLASIA Brief report Intronic BCL-6 mutations are preferentially targeted to the translocated allele in t(3;14)(q27;q32) non-hodgkin B-cell lymphoma Fabrice Jardin, Christian Bastard, Nathalie Contentin,
More informationMixed Phenotype Acute Leukemias
Mixed Phenotype Acute Leukemias CHEN GAO; AMY M. SANDS; JIANLAN SUN NORTH AMERICAN JOURNAL OF MEDICINE AND SCIENCE APR 2012 VOL 5 NO.2 INTRODUCTION Most cases of acute leukemia can be classified based
More informationWAO9 P-32 August 1, 2008 Bank Characterization Report
WAO9 P-32 August 1, 2008 Bank Characterization Report Cell Line description 3 Karyotype.. 4 5 Fluorescent in Situ Hybridization 6 7 Teratoma Assay 8 10 Flow Cytometry.. 11 Post Thaw Recovery 12 2 Cell
More informationIdentification of a commonly deleted region at 17p13.3 in leukemia and lymphoma associated with 17p abnormality
Leukemia (1998) 12, 510 516 1998 Stockton Press All rights reserved 0887-6924/98 $12.00 http://www.stockton-press.co.uk/leu Identification of a commonly deleted region at 17p13.3 in leukemia and lymphoma
More informationCHAPTER-VII : SUMMARY AND CONCLUSIONS
CHAPTER-VII : SUMMARY AND CONCLUSIONS 199 SUMMARY AND CONCLUSIONS t The rapid development of human genetics during the past couple of decades and the discovery of numerous cytogenetic abnormalities have
More informationPrimary Cutaneous Follicle Center Lymphoma Associated With an Extracutaneous Dissemination
AJCP / Case Report Primary Cutaneous Follicle Center Lymphoma Associated With an Extracutaneous Dissemination A Cytogenetic Finding of Potential Prognostic Value Shivakumar Subramaniyam, PhD, Cynthia M.
More informationAmerican Society of Cytopathology Core Curriculum in Molecular Biology
American Society of Cytopathology Core Curriculum in Molecular Biology American Society of Cytopathology Core Curriculum in Molecular Biology Chapter 1 Molecular Basis of Cancer Molecular Oncology Keisha
More informationKaryology. Preparation and study of karyotypes is part of Cytogenetics.
Chromosomal Karyotyping Karyology Karyotyping - process of pairing and ordering all chromosomes of an organism, thus providing a genome-wide snapshot of an individual's chromosomes. Karyotypes describe
More informationQuality in Control ALK-Lung Analyte Control (EML4-ALK) ALK-Lymphoma Analyte Control (NPM-ALK)
Quality in Control ALK-Lung Analyte Control (EML4-ALK) ALK-Lymphoma Analyte Control (NPM-ALK) 10 Product Codes: HCL007, HCL008 and HCL009 HCL010, HCL011 and HCL012 Page 1 of Contents 1. What is ALK?...
More informationTest Name Results Units Bio. Ref. Interval. Positive
LL - LL-ROHINI (NATIONAL REFERENCE 135091534 Age 36 Years Gender Female 1/9/2017 120000AM 1/9/2017 105316AM 2/9/2017 104147AM Ref By Final LEUKEMIA GENETIC ROFILE ANY SIX MARKERS, CR QUALITATIVE AML ETO
More informationObjectives. Morphology and IHC. Flow and Cyto FISH. Testing for Heme Malignancies 3/20/2013
Molecular Markers in Hematologic Malignancy: Ways to locate the needle in the haystack. Objectives Review the types of testing for hematologic malignancies Understand rationale for molecular testing Marcie
More informationAn Overview of Cytogenetics. Bridget Herschap, M.D. 9/23/2013
An Overview of Cytogenetics Bridget Herschap, M.D. 9/23/2013 Objectives } History and Introduction of Cytogenetics } Overview of Current Techniques } Common cytogenetic tests and their clinical application
More informationMalignant lymphomas are neoplasms that arise from B
Overview of the Role of Molecular Methods in the Diagnosis of Malignant Lymphomas L. Jeffrey Medeiros, MD; Jeanne Carr, PhD Objective. To review the role of molecular genetics in the diagnosis of malignant
More informationMyelodysplastic Syndrome Case 158
Myelodysplastic Syndrome Case 158 Dong Chen MD PhD Division of Hematopathology Mayo Clinic Clinical History 86 year old man Persistent borderline anemia and thrombocytopenia. His past medical history was
More informationCase Report Blasts-more than meets the eye: evaluation of post-induction day 21 bone marrow in CBFB rearranged acute leukemia
Int J Clin Exp Pathol 2014;7(7):4498-4502 www.ijcep.com /ISSN:1936-2625/IJCEP0000851 Case Report Blasts-more than meets the eye: evaluation of post-induction day 21 bone marrow in CBFB rearranged acute
More informationof TERT, MLL4, CCNE1, SENP5, and ROCK1 on tumor development were discussed.
Supplementary Note The potential association and implications of HBV integration at known and putative cancer genes of TERT, MLL4, CCNE1, SENP5, and ROCK1 on tumor development were discussed. Human telomerase
More informationMolecular Pathology of Lymphoma (Part 1) Rex K.H. Au-Yeung Department of Pathology, HKU
Molecular Pathology of Lymphoma (Part 1) Rex K.H. Au-Yeung Department of Pathology, HKU Lecture outline Time 10:00 11:00 11:15 12:10 12:20 13:15 Content Introduction to lymphoma Review of lymphocyte biology
More informationFrom Morphology to Molecular Pathology: A Practical Approach for Cytopathologists Part 1-Cytomorphology. Songlin Zhang, MD, PhD LSUHSC-Shreveport
From Morphology to Molecular Pathology: A Practical Approach for Cytopathologists Part 1-Cytomorphology Songlin Zhang, MD, PhD LSUHSC-Shreveport I have no Conflict of Interest. FNA on Lymphoproliferative
More informationNew chromosomal alterations in a series of 23 splenic marginal zone lymphoma patients revealed by Spectral Karyotyping (SKY)
Available online at www.sciencedirect.com Leukemia Research 32 (2008) 727 736 New chromosomal alterations in a series of 23 splenic marginal zone lymphoma patients revealed by Spectral Karyotyping (SKY)
More informationNEW YORK STATE DEPARTMENT OF HEALTH CLINICAL LABORATORY EVALUATION PROGRAM. Crosswalk of Proposed Revisions to Cytogenetics Standards
2014 Standard 2014 Guidance 2016 Standard 2016 Guidance Cytogenetics Standard 1 (CG S1) The laboratory shall request clinical information necessary for proper initiation of test procedures and interpretation
More informationCorporate Medical Policy. Policy Effective February 23, 2018
Corporate Medical Policy Genetic Testing for FLT3, NPM1 and CEBPA Mutations in Acute File Name: Origination: Last CAP Review: Next CAP Review: Last Review: genetic_testing_for_flt3_npm1_and_cebpa_mutations_in_acute_myeloid_leukemia
More informationThe role of cytogenomics in the diagnostic work-up of Chronic Lymphocytic Leukaemia
The role of cytogenomics in the diagnostic work-up of Chronic Lymphocytic Leukaemia Adrian Zordan, Meaghan Wall, Ruth MacKinnon, Pina D Achille & Lynda Campbell Victorian Cancer Cytogenetics Service (VCCS)
More informationHEMATOPATHOLOGY SUMMARY REPORT RL;MMR;
HEMATOPATHOLOGY SUMMARY REPORT RL;MMR; Page 1 of 1 05/15/20XX HP000000-20XX 05/21/20XX (212) 123-457 (51) 32-3455 (51) 123-457 Age: 78 DOB: 0/05/19XX SS#: 45-45-45 Clinical Information: 78 y/o female with
More information2013 AAIM Pathology Workshop
2013 AAIM Pathology Workshop John Schmieg, M.D., Ph.D. None Disclosures 1 Pathology Workshop Objectives Define the general philosophy of reviewing pathology reports Review the various components of Bone
More information