BRAF mutations characterize colon but not gastric cancer with mismatch repair deficiency
|
|
- Britton Scott
- 6 years ago
- Views:
Transcription
1 (2003) 22, & 2003 Nature Publishing Group All rights reserved /03 $ BRAF mutations characterize colon but not gastric cancer with mismatch repair deficiency Carla Oliveira 1, Mafalda Pinto 1, Alex Duval 2, Caroline Brennetot 2, Enric Domingo 3, Eloi Espı n 3, Manel Armengol 3, Hiroyuki Yamamoto 4, Richard Hamelin 2, Raquel Seruca 1 and Simo Schwartz Jr*,3 ONCOGENOMICS 1 Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Porto , Portugal; 2 INSERM U434 CEPH, Paris 75010, France; 3 Molecular Pathology Program, Centre d Investigacions en Bioquímica i Biologia Molecular (CIBBIM), Passeig Vall d Hebron , Barcelona 08035, Spain; 4 First Department of Internal Medicine, Sapporo Medical University, S.1, W.16, Chuo-ku, Sapporo , Japan Genes from the RAF family are Ras-regulated kinases involved in growth cellular responses. Recently,a V599E hotspot mutation within the BRAF gene was reported in a high percentage of colorectal tumors and significantly associated to defective mismatch repair (MMR). Additionally,BRAF mutations were described only in K-Rasnegative colon carcinomas,suggesting that BRAF/K-Ras activating mutations might be alternative genetic events in colon cancer. We have addressed to what extent the tumorigenic-positive selection exerted by BRAF mutations seen in colorectal MMR-deficient tumors was also involved in the tumorigenesis of gastric cancer. Accordingly,BRAF mutations were detected in 34% (25/74) of colorectal MMR-deficient tumors and in 5% (7/142) of MMR-proficient colorectal cases (P ¼ ). All mutations found in the MSI cases corresponded to the previously reported hotspot V599E. Two D593K and a K600E additional mutations were also detected in three MSS cases. However,only one mutation of BRAF was found within 124 MSS gastric tumors and none in 37 MSI gastric tumors,clearly suggesting that BRAF mutations are not involved in gastric tumorigenesis. Nonetheless,a high incidence of mutations of K-Ras was found within the MSI gastric group of tumors (P ¼ ),suggesting that the activation of K-Ras-dependent pathways contributes to the tumorigenesis of gastric cancers with MMR deficiency. Accordingly,our results show evidences that BRAF mutations characterize colon but not gastric tumors with MMR deficiency and are not involved in the tumorigenesis of gastric cancer of the mutator phenotype pathway. (2003) 22, doi: /sj.onc Keywords: genomic instability; BRAF; K-Ras; DNA mismatch repair; mutator phenotype; gastrointestinal cancer *Correspondence: S Schwartz; sschwartz@vhebron.net Received 15 April 2003; revised 30 July 2003; accepted 31 July 2003 Introduction Approximately 15% of sporadic colorectal and gastric tumors show microsatellite instability due to defects in their DNA mismatch repair (MMR) system. In both tumor types, this molecular phenotype is associated with a particular clinicopathological behavior, and characterized by an underlying genomic instability and a specific profile of target gene mutations (Aaltonen et al., 1993; Ionov et al., 1993; Thibodeau et al., 1993; Perucho, 1996). Moreover, several evidences have shown that stomach and colon tumors with microsatellite instability share the same target genes of the mutator phenotype, with similar mutational incidences (Yamamoto et al., 1997, 1999; Schwartz et al., 1999; Duval and Hamelin, 2002). Recently, a high incidence of activating mutations in BRAF, a gene from the Rasregulated kinase-encoding RAF family, has been found in colorectal tumors and associated to MMR-deficient cases (Davies et al., 2002; Rajagopalan et al., 2002; Yuen et al., 2002). Further, BRAF data showed a mutational hotspot in nucleotide 1796 within exon 15, accounting for a T:A transversion mutation and a valine to glutamic acid substitution, which is the most frequent somatic substitution ever identified in MMR-deficient colon cancers. In addition, these mutations were inversely associated to K-Ras mutations, reinforcing the idea that colorectal tumors with defective MMR progress through the same Ras/Raf/MAPK pathway than MMR-proficient tumors (Rajagopalan et al., 2002). However, it is not clear if colon and gastric tumors of the mutator phenotype share the alterations of the Ras/RAF/MAPK genes found in MMR-deficient colon tumors, nor if K-Ras and BRAF genes are also alternative genetic events in gastric cancer. Here, we show evidences to support that K-Ras but not BRAF mutations contribute to the tumorigenesis of MMR-deficient gastric cancer and therefore that K-Ras and BRAF mutations are not alternative genetic events in gastric cancer. Further, we also conclude that although MMR-deficient gastrointestinal tumors share the same mutational profile of the target genes of the mutator phenotype, they differ concerning
2 oncogenic mutations in genes from the Ras/RAF/ MAPK pathway. Results and discussion It has been recently shown that the V599E mutation of BRAF, the most common BRAF mutation found within colorectal tumors, has a transforming and oncogenic activity in NIH3T3 cells 138 times over wild-type BRAF (Davies et al., 2002). The presence of BRAF mutations in a high percentage of colorectal MMR-deficient carcinomas suggests its tumorigenic involvement within these tumors, and also its capability to induce tumor cell clonal expansions. Further, the absence of concomitant K-Ras and BRAF mutations in these tumors has suggested that both are alternative genetic events in colorectal tumorigenesis, and also that alterations within the Ras/RAF/MAPK pathway characterize MMR-proficient and -deficient colorectal tumors accordingly (Rajagopalan et al., 2002). In agreement with these findings, BRAF and K-Ras mutations were, respectively, detected in 34% (25/74) and 18% (11/60) of tumors from our collection of MSI colorectal cases (Figures 1 and 2). Further, all BRAF mutations detected corresponded to the V599E hotspot substitution reported by Davies et al. (2002) and were clearly associated to the presence of MMR deficiency (P ¼ ). In fact, only 5% (7/142) of colorectal MSS tumors showed BRAF mutations, from which four (57%) were V599E, one K600E and two D593K (Figures 1 and 2). As expected, the analysis of K-Ras showed higher mutational frequencies in colorectal MSS 9193 Figure 1 Mutation analysis of BRAF and K-Ras in colon and gastric carcinoma cases. SSCP/HA from BRAF are shown. DGGE analysis of K-Ras is also shown. N, normal tissue counterpart; T, tumor. BRAF mutations and wild-type sequence (normal) are indicated on top and abnormal bands pointed by arrows. (a) A representative SSCP/HA analysis of V599E BRAF mutations within MSI colorectal tumors. The corresponding mutated sequence is also shown at the right side. (b) A representative SSCP/HA analysis of BRAF mutations in MSS colorectal tumors. Two additional D593K and one K600E mutations were detected in the HA analysis and also by automatic sequencing (right). (c) SSCP/HA analysis of BRAF in MSS (left panel) and MSI (right panel) gastric carcinomas. Sequencing analysis of the single V599E BRAF mutation found in an MSS gastric tumor is also shown (right side). (d) Representative DGGE analysis of K-Ras in MSI gastric tumors. HAs corresponding to G12D and G13D mutations were found in several MSI tumor cases (arrows). A normal case is shown on the left. Two G12V mutations were also detected by automatic sequencing. Sequences are also shown. Additional V599E BRAF mutations were also detected in our collection of gastrointestinal tumor cell lines, including three MSI colon cell lines (Co115, RKO and LS411), two MSS colon cell lines (WIDR and HT29) and one MSI gastric cell line (St2957). No mutations were detected in other cell lines from the colon, including nine MSI (LS174 T, LoVo, TC71, HCT15, HCT116, TC7, SW48, HCT8 and KM12) and 19 MSS (GLY, EB, Isreco1, LS513, CBS, FET, V9P, ALA, FRI, LS1034, Isreco2, Colo320, Isreco3, SW480, SW1116, Colo205, SW620, CaCo2 and T84), neither in the MSI gastric cell line SNU1 nor in the MSS gastric cell lines GTL16, SNU16, KatoIII, MKN28, N87, TMK1, MKN1, MKN74, HGT1, AGS, MKN45, GP220, GP202 and L195
3 9194 Figure 2 Comparative analysis of the mutation frequencies of BRAF and K-Ras in MSS and MSI colon and gastric tumors. The upper part of the figure represents the mutation frequency of BRAF mutations in colon (light bars) and gastric (dark bars) in MSS and MSI tumors. The lower part of the figure represents the mutation frequency of K-Ras mutations in colon (light bars) and gastric (dark bars) in MSS and MSI tumors (38%, 28/73) tumors than in MSI (18%, 11/60) colorectal cases (P ¼ 0.01) (Figure 2). Mutations in both genes were also detected in a variety of colorectal MSS and MSI tumor cell lines (data not shown see legend of Figure 1). In the series of MSI (n ¼ 60) and MSS (n ¼ 73) colon tumors that were analysed for both genes, 50% of MSI and 41% of MSS cases show activating mutations of K-Ras or V599E BRAF mutations or both (Figure 3). These results clearly link the activation of the Ras/RAF/MAPK pathway in colorectal tumorigenesis to the oncogenic activation of K-Ras or BRAF genes (Figure 3). Even though K-Ras and BRAF mutations have been described as alternative events in these tumors (Rajagopalan et al., 2002), we found two concomitant mutations in two Japanese cases of our collection (Figure 3). These results might suggest either a possible synergistic contribution of both genes to the tumorigenic clonal expansion of these cases or a heterogeneous clonal population of cells within these tumors. Further analysis also revealed that the colorectal Japanese cases (n ¼ 22) from our collection showed higher levels of BRAF mutations (11/22, 50%) than tumors from European origin (14/52, 27%) (P ¼ 0.05), even though similar levels of K-Ras mutations were detected in both groups (data not shown). These results might suggest a modulation of the tumorigenic contribution from the Ras/RAF/MAPK pathway activation by the genetic ethnical background. Further, because stomach tumors of the mutator phenotype share similar target genes than colorectal tumors (Yamamoto et al., 1997, 1999; Schwartz et al., 1999; Duval and Hamelin, 2002), we did investigate whether BRAF mutations are also involved in gastric MMR-deficient cancer. However, no significant mutations were found in our collection of stomach primary tumors, including 37 MSI gastric primary tumors (Figures 1 and 2). In fact, we only detected a V599E mutation in an MSS tumor (1/124, 0.8%) within our series. These data led us to the conclusion that BRAF mutations are not involved in gastric tumorigenesis. However, as we have recently reported (Brennetot et al., in press), a high incidence of K-Ras mutations was found in tumors from the MSI group (10/36, 28%) of our gastric tumor collection whereas no mutations were detected in any of the MSS cases (P ¼ ), clearly suggesting that the activation of K-Ras contributes to the tumorigenesis of gastric cancer of the mutator phenotype, but not to MSS gastric cancer (Figures 2 and 3). Further, these data also support that K-Ras and BRAF mutations are not alternative events in gastric cancer. Further, although MMR-deficient colon and gastric tumors show a similar spectrum of mutations regarding the typical target genes of the mutator phenotype, they differ in the oncogenic mutational incidences found in genes from the Ras/RAF/MAPK pathway (Figure 4), raising the question of whether alternative K-Ras-depending pathways, other than the classical Figure 3 Comparative analysis of the percentage of cases harboring activating K-Ras and/or V599E BRAF mutations in colon and gastric MSS and MSI tumors. The upper bar represents the percentage of MSS and MSI colon carcinoma cases harboring activating K-Ras (light gray) and V599E BRAF (dark gray) or both (black). The lower bar represents the percentage of MSS gastric carcinoma cases harboring the V599E BRAF (dark gray) and the percentage of MSI gastric carcinoma cases harboring activating K-Ras (light gray). Cases without activating K-Ras and/or V599E BRAF, including K600E and D593K BRAF, are represented in white
4 tumor tissue or from macrodissected areas with at least 50% of tumor cells. Our collection of tumors and cell lines was analysed for microsatellite instability, using the mononucleotide repeats BAT-26 and BAT-25, and also a panel of dinucleotide repeat sequences, as previously described (Hoang et al., 1997; Boland et al., 1998; Oliveira et al., 1998; Yamamoto et al., 2001). We gather for this study 124 tumors and cell lines with MMR deficiency (74 sporadic colon carcinomas, including 22 cases from Japan, and also 37 sporadic gastric carcinomas, 12 colon cancer cell lines and one gastric cancer cell line), and 302 MMR-proficient tumors and cell lines (142 sporadic colon carcinomas, 124 sporadic gastric carcinomas, 21 colon cancer cell lines and 15 gastric cancer cell lines). All tumors and cell lines classified as MSI showed additional mutations in several target genes of the mutator phenotype, including hmsh3, hmsh6, BAX and TGFbRII (not shown) Figure 4 Mutation frequencies observed at BRAF, K-Ras and at coding repeat sequences in MSI sporadic colorectal (dark gray) and MSI gastric tumors (light gray). *Significant differences found between MSI colon and gastric tumors Ras/RAF/MAPK, might also be activated during gastric MMR-deficient tumorigenesis. Future research will have to answer to this possibility. Materials and methods Tissue samples and microsatellite instability analysis Tumors were obtained from the Hospital of S. Joa o (Porto, Portugal), the Saint-Antoine Hospital (Paris, France), the Sapporo Medical University (Sapporo, Japan) and from the Centre d Investigacions en Bioquimica i Biologia Molecular Vall d Hebron (CIBBIM) (Barcelona, Spain). Sample collection was carried out in accordance with previously established ethical protocols. Collected tumors were immediately frozen in liquid nitrogen for further analysis. Human cancer cell lines were obtained from different sources, including the American Type Culture Collection and the Japanese Cancer Research Resources Bank in Osaka, Japan. Gastric cell lines GP202, GP220 and L195 were established at the IPATIMUP. Some of the cell lines were previously characterized for a number of genetic alterations (Gayet et al., 2001). A family history was obtained for every carcinoma case. None of the patients included in the present study had a family history suggestive of hereditary nonpolyposis colorectal cancer. Hematoxylin- and eosin-stained sections were used to classify the tumors and allowed their macrodissection. High molecular weight DNA was isolated using standard methods from total sections of the tumors whenever tumor cells occupied more than 50% of BRAF and K-Ras mutation screening Mutational analysis of BRAF was performed by singlestranded conformation polymorphism and heteroduplex analysis (SSCP/HA). The fragment encompassing exon 15 was amplified by PCR in 376 carcinoma samples and 48 cell lines. Primer sequences and PCR conditions were based on those reported previously (Davies et al., 2002). Genomic DNA ( ng) was amplified by PCR using the following cycling conditions: 30 s at 941C, 30 s at 601C and 45 s at 721C for 35 cycles. Reaction products were diluted with denaturing buffer (formamide with 0.025% xylene cyanol and 0.025% bromophenol blue) and heated up to 991C for 10 min before being loaded onto 0.8 mutation detection enhancement gels (MDE Flowgen, Rockland, ME, USA), run at 81C for h and stained with silver nitrate. Selected bands were recovered from the gels and submitted to PCR reamplification with the original primer sets. Reamplified products were purified and sequenced on an ABI Prism 377 automatic sequencer (Perkin-Elmer, Foster City, CA, USA) using the ABI Prism Dye Terminator Cycle Sequencing Kit (Perkin- Elmer). All detected mutations were confirmed in a second independent PCR. K-Ras mutations were screened in 133 colorectal tumors (73 MSS and 60 MSI) and in 77 gastric carcinomas (42 MSS and 35 MSI). Mutational analysis of the K-Ras gene was performed by denaturing gradient gel electrophoresis (DGGE) as described (Gayet et al., 2001). Acknowledgements This work was supported by Grant FIS 01/1350 from the Spanish Fondo de Investigaciones Sanitarias and Fundac a o para a Cieˆ ncia e a Tecnologia, Portugal (Project: POCTI/ 35374/CBO/2000 and POCTI/CBO/40820/2001). References Aaltonen LA, Peltomaki P, Leach FS, Sistonen P, Pylkkanen L, Mecklin JP, Jarvinen H, Powell SM, Jen J, Hamilton SR, Petersen GM, Kinzler KW, Vogelstein B and de la Chapelle A. (1993). Science, 260, Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, Meltzer SJ, Rodrigues-Bigas MA, Fodde R, Ranzani GN and Srivastava S. (1998). Cancer Res., 58, Brennetot C, Pinto M, Oliveira C, Schwartz Jr S, Seruca R, Duval A and Hamelin R: Gastroenterology. (in press). Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard- Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JWC, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster
5 9196 R, Stratton MR and Futreal PA. (2002). Nature, 417, Duval A and Hamelin R. (2002). Cancer Res., 62, Gayet J, Zhou XP, Duval A, Rolland S, Hoang JM, Cottu P and Hamelin R. (2001)., 20, Hoang JM, Cottu PH, Thuille B, Salmon RJ, Thomas G and Hamelin R. (1997). Cancer Res., 57, Ionov Y, Peinado MA, Malkhosyan S, Shibata D and Perucho M. (1993). Nature, 363, Oliveira C, Seruca R, Seixas M and Sobrinho-Simo es M. (1998). Am. J. Pathol., 153, Perucho M. (1996). J. Biol. Chem., 377, Rajagopalan H, Bardelli A, Lengauer C, Kinzler KW, Vogelstein B and Velculescu VE. (2002). Nature, 418, 934. Schwartz Jr S, Yamamoto H, Navarro M, Maestro M, Revento s J and Perucho M. (1999). Cancer Res., 59, Thibodeau SN, Bren G and Schaid D. (1993). Science, 260, Yamamoto H, Fukushima H, Itoh F, Horiuchi S, Min Y, Iku S and Imai K. (2001). J. Exp. Clin. Cancer Res., 20, Yamamoto H, Perez-Piteira J, Yoshida T, Terada M, Itoh F, Imai K and Perucho M. (1999). Gastroenterology, 116, Yamamoto H, Sawai H and Perucho M. (1997). Cancer Res., 57, Yuen ST, Davies H, Chan TL, Ho JW, Bignell GR, Cox C, Stephens P, Edkins S, Tsui WW, Chan AS, Futreal PA, Stratton MR, Wooster R and Leung SY. (2002). Cancer Res., 62,
Clinicopathologic Characteristics of Left-Sided Colon Cancers with High Microsatellite Instability
The Korean Journal of Pathology 29; 43: 428-34 DOI: 1.4132/KoreanJPathol.29.43.5.428 Clinicopathologic Characteristics of Left-Sided Colon Cancers with High Microsatellite Instability Sang Kyum Kim Junjeong
More informationKeywords: microsatellite instability; multiple primary cancer; hereditary non-polyposis colorectal cancer
790 Gut 2000;46:790 794 First Department of Internal Medicine, Sapporo Medical University, Sapporo, K Yamashita Y Arimura S Kurokawa F Itoh T Endo K Imai First Department of Surgery, Sapporo Medical University,
More informationLynch Syndrome Screening for Endometrial Cancer: Basic Concepts 1/16/2017
1 Hi, my name is Sarah Kerr. I m a pathologist at Mayo Clinic, where I participate in our high volume Lynch syndrome tumor testing practice. Today I hope to cover some of the basics needed to understand
More informationExtensive characterization of genetic alterations in a series of human colorectal cancer cell lines
(2001) 20, 5025 ± 5032 ã 2001 Nature Publishing Group All rights reserved 0950 ± 9232/01 $15.00 www.nature.com/onc Extensive characterization of genetic alterations in a series of human colorectal cancer
More informationMSI-L Gastric Carcinomas Share the hmlh1 Methylation Status of MSI-H Carcinomas but Not Their Clinicopathological Profile
0023-6837/00/8012-1915$03.00/0 LABORATORY INVESTIGATION Vol. 80, No. 12, p. 1915, 2000 Copyright 2000 by The United States and Canadian Academy of Pathology, Inc. Printed in U.S.A. MSI-L Gastric Carcinomas
More informationTumors of the microsatellite mutator phenotype (MMP)
Mutational inactivation of the proapoptotic gene BAX confers selective advantage during tumor clonal evolution Yurij Ionov, Hiroyuki Yamamoto, Stanislaw Krajewski, John C. Reed, and Manuel Perucho* The
More informationRobust microsatellite instability (MSI) analysis by denaturing high-performance liquid chromatography (DHPLC)
J Hum Genet (2003) 48:525 530 DOI 10.1007/s10038-003-0070-y ORIGINAL ARTICLE Il-Jin Kim Æ Yong Shin Æ Hio Chung Kang Jae-Hyun Park Æ Ja-Lok Ku Æ Hye-Won Park Hye-Rin Park Æ Seok-Byung Lim Seung-Yong Jeong
More informationA Review from the Genetic Counselor s Perspective
: A Review from the Genetic Counselor s Perspective Erin Sutcliffe, MS, CGC Certified Genetic Counselor Cancer Risk Evaluation Program INTRODUCTION Errors in base pair matching that occur during DNA replication,
More informationONCOGENOMICS. KRAS and BRAF oncogenic mutations in MSS colorectal carcinoma progression
(2007) 26, 158 163 & 2007 Nature Publishing Group All rights reserved 0950-9232/07 $30.00 www.nature.com/onc ONCOGENOMICS KRAS and BRAF oncogenic mutations in MSS colorectal carcinoma progression C Oliveira
More informationAnatomic Molecular Pathology: An Emerging Field
Anatomic Molecular Pathology: An Emerging Field Antonia R. Sepulveda M.D., Ph.D. University of Pennsylvania asepu@mail.med.upenn.edu 2008 ASIP Annual Meeting Anatomic pathology (U.S.) is a medical specialty
More informationDevelopment of Carcinoma Pathways
The Construction of Genetic Pathway to Colorectal Cancer Moriah Wright, MD Clinical Fellow in Colorectal Surgery Creighton University School of Medicine Management of Colon and Diseases February 23, 2019
More informationCAP Laboratory Improvement Programs. Summary of Microsatellite Instability Test Results From Laboratories Participating in Proficiency Surveys
CAP Laboratory Improvement Programs Summary of Microsatellite Instability Test Results From Laboratories Participating in Proficiency Surveys Proficiency Survey Results From 2005 to 2012 Theresa A. Boyle,
More informationDetection of Microsatellite Instability by Fluorescence Multiplex Polymerase Chain Reaction
Journal of Molecular Diagnostics, Vol. 2, No. 1, February 2000 Copyright American Society for Investigative Pathology and the Association for Molecular Pathology Detection of Microsatellite Instability
More informationAn Optimized Pentaplex PCR for Detecting DNA Mismatch Repair-Deficient Colorectal Cancers
An Optimized Pentaplex PCR for Detecting DNA Mismatch Repair-Deficient Colorectal Cancers Ajay Goel 1 *., Takeshi Nagasaka 1., Richard Hamelin 2, C. Richard Boland 1 * 1 Division of Gastroenterology, Department
More informationBRAF Mutations in Aberrant Crypt Foci and Hyperplastic Polyposis
American Journal of Pathology, Vol. 166, No. 4, April 2005 Copyright American Society for Investigative Pathology Gastrointestinal, Hepatobiliary and Pancreatic Pathology BRAF Mutations in Aberrant Crypt
More informationASSESSMENT OF MLH1 PROMOTER METHYLATION IN ENDOMETRIAL CANCER USING PYROSEQUENCING TECHNOLOGY OBJECTIVES
ASSESSMENT OF MLH1 PROMOTER METHYLATION IN ENDOMETRIAL CANCER USING PYROSEQUENCING TECHNOLOGY Authors: Duilio Della Libera, Alessandra D Urso, Federica Modesti, Georgeta Florea, Marta Gobbato Hospital:
More informationColorectal cancer Chapelle, J Clin Oncol, 2010
Colorectal cancer Chapelle, J Clin Oncol, 2010 Early-Stage Colorectal cancer: Microsatellite instability, multigene assay & emerging molecular strategy Asit Paul, MD, PhD 11/24/15 Mr. X: A 50 yo asymptomatic
More informationUnmasking the role of KRAS and BRAF pathways in MSI colorectal tumors
Unmasking the role of KRAS and BRAF pathways in MSI colorectal tumors Expert Rev. Gastroenterol. Hepatol. 3(1), 5 9 (2009) Raquel Seruca, MD, PhD Author for correspondence Instituto de Patologia e Imunologia
More informationMicrosatellite instability in colorectal-cancer patients with suspected genetic predisposition.
Chapter 3 Microsatellite instability in colorectal-cancer patients with suspected genetic predisposition. Calistri D, Presciuttini S, Buonsanti G, Radice P, Gazzoli I, Pensotti V, Sala P, Eboli M, Andreola
More informationMicrosatellite Instability and Mismatch Repair Protein (hmlh1, hmsh2) Expression in Intrahepatic Cholangiocarcinoma
The Korean Journal of Pathology 2005; 39: 9-14 Microsatellite Instability and Mismatch Repair Protein (hmlh1, hmsh2) Expression in Intrahepatic Cholangiocarcinoma Yun Kyung Kang Woo Ho Kim 1 Department
More informationHanna Vauhkonen and Antti Sajantila Department of Forensic Medicine, University of Helsinki, Helsinki, Finland.
Short Communication Genetics and Molecular Biology, 29, 4, 608-612 (2006) Copyright by the Brazilian Society of Genetics. Printed in Brazil www.sbg.org.br Intrinsic structural variation of the complex
More informationA role for p300 CREB binding protein genes in promoting cancer progression in colon cancer cell lines with microsatellite instability
A role for p300 CREB binding protein genes in promoting cancer progression in colon cancer cell lines with microsatellite instability Yurij Ionov*, Sei-Ichi Matsui, and John K. Cowell Department of Cancer
More informationInfrequent Microsatellite Instability in Urothelial Cell Carcinoma of the Bladder in Young Patients
european urology 49 (2006) 685 690 available at www.sciencedirect.com journal homepage: www.europeanurology.com Bladder Cancer Infrequent Microsatellite Instability in Urothelial Cell Carcinoma of the
More informationMTHFR C677T polymorphism and microsatellite instability in CRC 315
MTHFR C677T polymorphism and microsatellite instability in CRC 315 Relationship of the methylenetetrahydrofolate reductase C677T polymorphism with microsatellite instability and promoter hypermethylation
More informationFrequent alteration of DNA damage signalling and repair pathways in human colorectal cancers with microsatellite instability
(2007) 26, 5919 5926 & 2007 Nature Publishing Group All rights reserved 0950-9232/07 $30.00 www.nature.com/onc ORIGINAL ARTICLE Frequent alteration of DNA damage signalling and repair pathways in human
More informationColorectal carcinogenesis: MSI-H versus MSI-L
Disease Markers 20 (2004) 199 206 199 IOS Press Colorectal carcinogenesis: MSI-H versus MSI-L Timothy M. Pawlik, Chandrajit P. Raut and Miguel A. Rodriguez-Bigas Department of Surgical Oncology, The University
More informationWhite paper Evaluation of BRAF (V600E) Mutation by Immunohistochemical Staining with anti-braf V600E (VE1) Antibody: A Comparison with Sanger
White paper Evaluation of BRAF (V600E) Mutation by Immunohistochemical Staining with anti-braf V600E (VE1) Antibody: A Comparison with Sanger Sequencing 2 Evaluation of BRAF (V600E) Mutation by Immuno-histochemical
More informationEvaluation of tumor microsatellite instability in laryngeal cancer using five quasimonomorphic mononucleotide repeats and pentaplex PCR
Advances in Medical Sciences Vol. 53(1) 2008 pp 59-63 DOI: 10.2478/v10039-008-0023-y Medical University of Bialystok, Poland Evaluation of tumor microsatellite instability in laryngeal cancer using five
More informationMicrosatellite instability is a rare phenomenon in transition from chronic to blastic phase chronic myeloid leukemia
Turkish Journal of Cancer Vol.31/ No. 2/2001 Microsatellite instability is a rare phenomenon in transition from chronic to blastic phase chronic myeloid leukemia H. OGÜN SERCAN, ZEYNEP Y. SERCAN, SEFA
More informationGenetic Reconstruction of One Hereditary Nonpolyposis Colorectal Cancer History with Multiple Initiations of the Disease
The Open Environmental & Biological Monitoring Journal, 2008, 1, 43-47 43 Genetic Reconstruction of One Hereditary Nonpolyposis Colorectal Cancer History with Multiple Initiations of the Disease Open Access
More informationCover Page. The handle holds various files of this Leiden University dissertation.
Cover Page The handle http://hdl.handle.net/1887/22278 holds various files of this Leiden University dissertation. Author: Cunha Carvalho de Miranda, Noel Filipe da Title: Mismatch repair and MUTYH deficient
More informationThe New England Journal of Medicine
The New England Journal of Medicine Copyright, 1998, by the Massachusetts Medical Society VOLUME 338 M AY 21, 1998 NUMBER 21 INCIDENCE OF HEREDITARY NONPOLYPOSIS COLORECTAL CANCER AND THE FEASIBILITY OF
More informationAccumulated Clonal Genetic Alterations in Familial and Sporadic Colorectal Carcinomas with Widespread Instability in Microsatellite Sequences
American Journal of Pathology, Vol. 153, No. 4, October 1998 Copyright American Society for Investigative Pathology Accumulated Clonal Genetic Alterations in Familial and Sporadic Colorectal Carcinomas
More informationT he lifetime risk of developing colorectal cancer is 5%, with. Adenoma prevalence and cancer risk in familial non-polyposis colorectal cancer CANCER
228 CANCER Adenoma prevalence and cancer risk in familial non-polyposis colorectal cancer G Lindgren, A Liljegren, E Jaramillo, C Rubio, A Lindblom... See end of article for authors affiliations... Correspondence
More informationOrigin of Microsatellite Instability in Gastric Cancer
American Journal of Pathology, Vol. 155, No. 1, July 1999 Copyright American Society for Investigative Pathology Origin of Microsatellite Instability in Gastric Cancer Kevin C. Halling,* Jeffrey Harper,
More informationColorectal carcinoma (CRC) was traditionally thought of
Testing for Defective DNA Mismatch Repair in Colorectal Carcinoma A Practical Guide Lawrence J. Burgart, MD Context. Significant bench and clinical data have been generated during the last decade regarding
More informationCase Study. Overview. Deleterious MLH1 mutation detected on sequencing 10/16/2014
The Role of Next Generation Sequencing for Hereditary Cancer Syndromes: A Focus on Endometrial Cancer Laura J. Tafe, MD Assistant Professor of Pathology Assistant Director, Molecular Pathology Dartmouth-Hitchcock
More informationIncidence and functional consequences of hmlh1 promoter hypermethylation in colorectal carcinoma
Proc. Natl. Acad. Sci. USA Vol. 95, pp. 6870 6875, June 1998 Genetics Incidence and functional consequences of hmlh1 promoter hypermethylation in colorectal carcinoma JAMES G. HERMAN*, ASAD UMAR, KORNELIA
More informationOriginal article: Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran 2
Original article: EVALUATION OF MICROSATELLITE INSTABILITY IN TUMOR AND TUMOR MARGINAL SAMPLES OF SPORADIC COLORECTAL CANCER USING MONONUCLEOTIDE MARKERS Jafar Nouri Nojadeh 1, Shahriar Hashemzadeh 2,3,
More informationOriginal Article Frequent CpG island methylation: a risk factor in the progression of traditional serrated adenoma of the colorectum
Int J Clin Exp Pathol 2017;10(9):9666-9674 www.ijcep.com /ISSN:1936-2625/IJCEP0045970 Original Article Frequent CpG island methylation: a risk factor in the progression of traditional serrated adenoma
More informationHereditary non polyposis colorectal cancer in a random sample of colorectal cancer patients
Basic Science Hereditary non polyposis colorectal cancer in a random sample of colorectal cancer patients Nada Pavlović-Čalić 1, Izet Eminović 2, Vesna Hadžiabdić 3, Kasim Muminhodžić 1, Radovan Komel
More informationDetection of Microsatellite Instability in Colorectal Cancer Using an Alternative Multiplex Assay of Quasi-Monomorphic Mononucleotide Markers
Journal of Molecular Diagnostics, Vol. 10, No. 2, March 2008 Copyright American Society for Investigative Pathology and the Association for Molecular Pathology DOI: 10.2353/jmoldx.2008.070087 Detection
More informationReplication error phenotype, clinicopathological variables, and patient outcome in Dukes B stage II (T3,N0,M0) colorectal cancer
200 Department of Pathology, Royal College of Surgeons in Ireland, Dublin, Republic of Ireland B Curran EWKay M Leader Department of Biochemistry K Lenehan O Tighe M A Bennett D T Croke Gastroenterology
More informationMolecular Diagnosis for Colorectal Cancer Patients
Molecular Diagnosis for Colorectal Cancer Patients Antonia R. Sepulveda MD, PhD, FCAP October, 20, 2010 www.cap.org Welcome to the PHC Webinar Series This talk on The Molecular Diagnosis for Colorectal
More informationColon Cancer and Hereditary Cancer Syndromes
Colon Cancer and Hereditary Cancer Syndromes Gisela Keller Institute of Pathology Technische Universität München gisela.keller@lrz.tum.de Colon Cancer and Hereditary Cancer Syndromes epidemiology models
More informationMore than 40 years ago, 5-Fluorouracil (5-FU), was
GASTROENTEROLOGY 2004;126:394 401 RAPID COMMUNICATIONS Use of 5-Fluorouracil and Survival in Patients With Microsatellite-Unstable Colorectal Cancer JOHN M. CARETHERS,*,,, E. JULIETA SMITH, CYNTHIA A.
More informationHypermethylation of the hmlh1 gene promoter is associated with microsatellite instability in early human gastric neoplasia
(2001) 20, 329 ± 335 ã 2001 Nature Publishing Group All rights reserved 0950 ± 9232/01 $15.00 www.nature.com/onc Hypermethylation of the hmlh1 gene promoter is associated with microsatellite instability
More informationTumor Microsatellite-Instability Status as a Predictor of Benefit from Fluorouracil-Based Adjuvant Chemotherapy for Colon Cancer
original article Tumor Microsatellite-Instability Status as a Predictor of Benefit from Fluorouracil-Based Adjuvant Chemotherapy for Colon Cancer Christine M. Ribic, M.Sc., Daniel J. Sargent, Ph.D., Malcolm
More informationWe are IntechOpen, the world s leading publisher of Open Access books Built by scientists, for scientists. International authors and editors
We are IntechOpen, the world s leading publisher of Open Access books Built by scientists, for scientists 3,350 108,000 1.7 M Open access books available International authors and editors Downloads Our
More informationSerrated Polyps and a Classification of Colorectal Cancer
Serrated Polyps and a Classification of Colorectal Cancer Ian Chandler June 2011 Structure Serrated polyps and cancer Molecular biology The Jass classification The familiar but oversimplified Vogelsteingram
More informationFamilial and Hereditary Colon Cancer
Familial and Hereditary Colon Cancer Aasma Shaukat, MD, MPH, FACG, FASGE, FACP GI Section Chief, Minneapolis VAMC Associate Professor, Division of Gastroenterology, Department of Medicine, University of
More informationColorectal carcinoma is the fourth most prevalent cancer
GASTROENTEROLOGY 2006;131:729 737 Prognostic Impact of Microsatellite Instability and DNA Ploidy in Human Colon Carcinoma Patients FRANK A. SINICROPE,*, RAFAELA L. REGO,* KEVIN C. HALLING, NATHAN FOSTER,
More informationColon cancer is thought to arise through the progressive
Epigenetic phenotypes distinguish microsatellitestable and -unstable colorectal cancers Shannon A. Kuismanen*, Mari T. Holmberg*, Reijo Salovaara*, Pascal Schweizer, Lauri A. Aaltonen*, Albert de la Chapelle,
More informationBiallelic inactivation of hmlh1 by epigenetic gene silencing, a novel mechanism causing human MSI cancers
Proc. Natl. Acad. Sci. USA Vol. 95, pp. 8698 8702, July 1998 Genetics Biallelic inactivation of hmlh1 by epigenetic gene silencing, a novel mechanism causing human MSI cancers MARTINA L. VEIGL*, LAKSHMI
More informationP rediction of a mismatch repair gene defect by microsatellite instability and immunohistochemical analysis in endometrial tumours from hnpcc patients
P rediction of a mismatch repair gene defect by microsatellite instability and immunohistochemical analysis in endometrial tumours from hnpcc patients Chapter 2 Wiljo J. F. de Leeuw, Jan Willem Dierssen,
More informationTable S1. Primers and PCR protocols for mutation screening of MN1, NF2, KREMEN1 and ZNRF3.
Table S1. Primers and PCR protocols for mutation screening of MN1, NF2, KREMEN1 and ZNRF3. MN1 (Accession No. NM_002430) MN1-1514F 5 -GGCTGTCATGCCCTATTGAT Exon 1 MN1-1882R 5 -CTGGTGGGGATGATGACTTC Exon
More informationStability of BAT26 in tumours of hereditary nonpolyposis colorectal cancer patients with MSH2 intragenic deletion
(2006) 14, 63 68 & 2006 Nature Publishing Group All rights reserved 1018-4813/06 $30.00 www.nature.com/ejhg ARTICLE Stability of BAT26 in tumours of hereditary nonpolyposis colorectal cancer patients with
More informationFamilial and Hereditary Colon Cancer
Familial and Hereditary Colon Cancer Aasma Shaukat, MD, MPH, FACG, FASGE, FACP GI Section Chief, Minneapolis VAMC Associate Professor, Division of Gastroenterology, Department of Medicine, University of
More informationThe Whys OAP Annual Meeting CCO Symposium September 20. Immunohistochemical Assessment Dr. Terence Colgan Mount Sinai Hospital, Toronto
Immunohistochemical Assessment of Mismatch Repair Proteins in Endometrial Cancer: The Whys and How Terence J. Colgan, MD Head of Gynaecological Pathology, Mount Sinai Hospital, University of Toronto, Toronto.
More information(a) Schematic diagram of the FS mutation of UVRAG in exon 8 containing the highly instable
Supplementary Figure 1. Frameshift (FS) mutation in UVRAG. (a) Schematic diagram of the FS mutation of UVRAG in exon 8 containing the highly instable A 10 DNA repeat, generating a premature stop codon
More informationOriginal Article Immunohistochemistry is highly sensitive and specific for detecting the BRAF V600E mutation in papillary thyroid carcinoma
Int J Clin Exp Pathol 2015;8(11):15072-15078 www.ijcep.com /ISSN:1936-2625/IJCEP0015697 Original Article Immunohistochemistry is highly sensitive and specific for detecting the BRAF V600E mutation in papillary
More informationSALSA MS-MLPA KIT ME011-A1 Mismatch Repair genes (MMR) Lot 0609, 0408, 0807, 0407
SALSA MS-MLPA KIT ME011-A1 Mismatch Repair genes (MMR) Lot 0609, 0408, 0807, 0407 The Mismatch Repair (MMR) system is critical for the maintenance of genomic stability. MMR increases the fidelity of DNA
More informationReview Article Relationship between DNA Mismatch Repair Deficiency and Endometrial Cancer
SAGE-Hindawi Access to Research Molecular Biology International Volume 2011, Article ID 256063, 6 pages doi:10.4061/2011/256063 Review Article Relationship between DNA Mismatch Repair Deficiency and Kenta
More informationTumor Microsatellite Instability in Early Onset Gastric Cancer
Journal of Molecular Diagnostics, Vol. 7, No. 4, October 2005 Copyright American Society for Investigative Pathology and the Association for Molecular Pathology Tumor Microsatellite Instability in Early
More informationMutations of BRAF and KRAS2 in the development of Barrett s adenocarcinoma
(2004) 23, 554 558 & 2004 Nature Publishing Group All rights reserved 0950-9232/04 $25.00 www.nature.com/onc Mutations of BRAF and KRAS2 in the development of Barrett s adenocarcinoma Florian Sommerer
More informationBRAF mutation in colorectal carcinomas with signet ring cell component
Cancer Biol Med 2017. doi: 10.20892/j.issn.2095-3941.2017.0053 ORIGINAL ARTICLE BRAF mutation in colorectal carcinomas with signet ring cell component Serap Yalcin 1, Onder Onguru 2 1 Department of Molecular
More informationLYNCH SYNDROME: IN YOUR FACE BUT LOST IN SPACE (MOUNTAIN)!
LYNCH SYNDROME: IN YOUR FACE BUT LOST IN SPACE (MOUNTAIN)! Kathryn Singh, MPH, MS, LCGC Associate Clinical Professor Assistant Director, Graduate Program in Genetic Counseling Division of Genetic and Genomic
More informationMeasure Description. Denominator Statement
CMS ID/CMS QCDR ID: CAP 18 Title: Mismatch Repair (MMR) or Microsatellite Instability (MSI) Biomarker Testing to Inform Clinical Management and Treatment Decisions in Patients with Primary or Metastatic
More informationFAMILIAL ADENOMATOUS POLYPOSIS: ANALYSIS OF GENETIC INSTABILITY OF MICROSATELLITES LOCI AND GENETIC ALTERNATIONS OF TUMOR SUPPRESSOR GENES
& FAMILIAL ADENOMATOUS POLYPOSIS: ANALYSIS OF GENETIC INSTABILITY OF MICROSATELLITES LOCI AND GENETIC ALTERNATIONS OF TUMOR SUPPRESSOR GENES Vesna Hadžiavdić¹, Izet Eminović¹, Mensura Aščerić²*, Radovan
More informationColorectal cancer susceptibility associated with the hmlh1 V384D variant
Molecular Medicine REPORTS 2: 887-891, 2009 Colorectal cancer susceptibility associated with the hmlh1 V384D variant TOMONORI OHSAWA 1,4, TOMOKO SAHARA 1,5, SHINO MURAMATSU 1,5, YOJI NISHIMURA 2, TOSHIMASA
More informationAmoyDx TM BRAF V600E Mutation Detection Kit
AmoyDx TM BRAF V600E Mutation Detection Kit Detection of V600E mutation in the BRAF oncogene Instructions For Use Instructions Version: B3.1 Date of Revision: April 2012 Store at -20±2 o C 1/5 Background
More informationCase Presentation Diana Lim, MBBS, FRCPA, FRCPath Senior Consultant Department of Pathology, National University Health System, Singapore Assistant Pr
Case Presentation Diana Lim, MBBS, FRCPA, FRCPath Senior Consultant Department of Pathology, National University Health System, Singapore Assistant Professor Yong Loo Lin School of Medicine, National University
More informationReview Article Clinicopathological Features and Management of Cancers in Lynch Syndrome
Pathology Research International Volume 2012, Article ID 350309, 6 pages doi:10.1155/2012/350309 Review Article Clinicopathological Features and Management of Cancers in Lynch Syndrome Markku Aarnio Department
More informationColorectal Cancer - Working in Partnership. David Baty Genetics, Ninewells Hospital
Colorectal Cancer - Working in Partnership David Baty Genetics, Ninewells Hospital Genetics and Pathology National initiatives Colorectal cancer Inherited CRC Sporadic CRC The Liquid Biopsy The future?
More informationCLINICAL FINDINGS WITH IMPLICATIONS FOR GENETIC TESTING IN FAMILIES WITH CLUSTERING OF COLORECTAL CANCER
CLINICAL FINDINGS WITH IMPLICATIONS FOR GENETIC TESTING IN FAMILIES WITH CLUSTERING OF COLORECTAL CANCER CLINICAL FINDINGS WITH IMPLICATIONS FOR GENETIC TESTING IN FAMILIES WITH CLUSTERING OF COLORECTAL
More informationBRAF mutations and phosphorylation status of mitogen-activated protein kinases in the development of flat and depressed-type colorectal neoplasias
British Journal of Cancer (2006) 94, 311 317 All rights reserved 0007 0920/06 $30.00 www.bjcancer.com BRAF mutations and phosphorylation status of mitogen-activated protein kinases in the development of
More informationHigh risk stage II colon cancer
High risk stage II colon cancer Joel Gingerich, MD, FRCPC Assistant Professor Medical Oncologist University of Manitoba CancerCare Manitoba Disclaimer No conflict of interests 16 October 2010 Overview
More informationGastric Carcinoma with Lymphoid Stroma: Association with Epstein Virus Genome demonstrated by PCR
Gastric Carcinoma with Lymphoid Stroma: Association with Epstein Virus Genome demonstrated by PCR Pages with reference to book, From 305 To 307 Irshad N. Soomro,Samina Noorali,Syed Abdul Aziz,Suhail Muzaffar,Shahid
More informationHereditary Non-Polyposis Colon Cancer and Microsatellite instability
Hereditary Non-Polyposis Colon Cancer and Microsatellite instability Byoung Kwon Kim M.D., M.S., IFCAP Department of Pathology and Medical Genetics Institute, Green Cross Reference Laboratory Agenda Long
More informationIntroduction. Why Do MSI/MMR Analysis?
Clinical Significance Of MSI, KRAS, & EGFR Pathway In Colorectal Carcinoma UCSF & Stanford Current Issues In Anatomic Pathology Introduction Microsatellite instability and mismatch repair protein deficiency
More informationThe role of hypermethylation of the hmlh1 promoter region in HNPCC versus MSI+ sporadic colorectal cancers
588 Cancer and Immunogenetics Laboratory, Imperial Cancer Research Fund, Institute of Molecular Medicine, John RadcliVe Hospital, Oxford OX3 9DU, UK J M D Wheeler W F Bodmer Department of Medical Genetics,
More informationColonic polyps and colon cancer. Andrew Macpherson Director of Gastroentology University of Bern
Colonic polyps and colon cancer Andrew Macpherson Director of Gastroentology University of Bern Improtance of the problem of colon cancers - Epidemiology Lifetime risk 5% Incidence/10 5 /annum (US Detroit
More informationChemotherapy induces genomic instability in oral mucosal cells of women with breast cancer
ORIGINAL ARTICLE Chemotherapy induces genomic instability in oral mucosal cells of women with breast cancer Patricia G. Coelho 1, Sarah R. Marsicano 1, Pamela O. Delgado 1, Jorge. L. F. Pinto 1, Aleksandra
More informationMSH6 germline mutations in early-onset colorectal cancer patients without family history of the disease
British Journal of Cancer (2006) 95, 752 756 All rights reserved 0007 0920/06 $30.00 www.bjcancer.com MSH6 germline mutations in early-onset colorectal cancer patients without family history of the disease
More informationMRC-Holland MLPA. Description version 29;
SALSA MLPA KIT P003-B1 MLH1/MSH2 Lot 1209, 0109. As compared to the previous lots 0307 and 1006, one MLH1 probe (exon 19) and four MSH2 probes have been replaced. In addition, one extra MSH2 exon 1 probe,
More informationCélia DeLozier-Blanchet
The Genetics Consultation in OB-GYN : Hereditary cancers Célia DeLozier-Blanchet Division of Medical Genetics, Geneva University Hospital It is probable that all cancers are genetic! genetic vs. hereditary
More informationHereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) in Argentina: Report from a Referral Hospital Register
Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) in Argentina: Report from a Referral Hospital Register Carlos A. Vaccaro, M.D., 1 Fernando Bonadeo, M.D., 1 Analía V. Roverano, M.D., 1 Paivi
More informationGenetic epidemiology of mutated K-ras proto-oncogene, altered suppressor genes, and microsatellite instability in colorectal adenomas
826 Gut 1999;44:826 833 Genetic epidemiology of mutated K-ras proto-oncogene, altered suppressor genes, and microsatellite instability in colorectal adenomas A Rashid, M Zahurak, S N Goodman, S R Hamilton
More informationThe Role of the CpG Island Methylator Phenotype on Survival Outcome in Colon Cancer
Gut and Liver, Vol. 9, No. 2, March 215, pp. 22-27 ORiginal Article The Role of the CpG Island Methylator Phenotype on Survival Outcome in Colon Cancer Ki Joo Kang*, Byung-Hoon Min, Kyung Ju Ryu, Kyoung-Mee
More informationGENETICS OF COLORECTAL CANCER: HEREDITARY ASPECTS By. Magnitude of the Problem. Magnitude of the Problem. Cardinal Features of Lynch Syndrome
GENETICS OF COLORECTAL CANCER: HEREDITARY ASPECTS By HENRY T. LYNCH, M.D. 1 Could this be hereditary Colon Cancer 4 Creighton University School of Medicine Omaha, Nebraska Magnitude of the Problem Annual
More informationMarcatori biomolecolari dei carcinomi del colon-retto sporadici ed ereditari
Marcatori biomolecolari dei carcinomi del colon-retto sporadici ed ereditari Milo Frattini XII Congresso AIFEG Villa Cagnola - Gazzada Schianno (VA) 16/17.10.2014 APC β-catenina APC Met (p16) Models of
More informationCOLORECTAL PATHWAY GROUP, MANCHESTER CANCER. Guidelines for the assessment of mismatch. Colorectal Cancer
COLORECTAL PATHWAY GROUP, MANCHESTER CANCER Guidelines for the assessment of mismatch repair (MMR) status in Colorectal Cancer March 2017 1 Background Mismatch repair (MMR) deficiency is seen in approximately
More informationH ereditary non-polyposis colorectal cancer (HNPCC;
405 CANCER Pathogenicity of missense and splice site mutations in hmsh2 and hmlh1 mismatch repair genes: implications for genetic testing M Cravo, A J Afonso, P Lage, C Albuquerque, L Maia, C Lacerda,
More informationPolicy Specific Section: Medical Necessity and Investigational / Experimental. October 14, 1998 March 28, 2014
Medical Policy Genetic Testing for Colorectal Cancer Type: Medical Necessity and Investigational / Experimental Policy Specific Section: Laboratory/Pathology Original Policy Date: Effective Date: October
More informationMolecular biology of colorectal cancer
Molecular biology of colorectal cancer Phil Quirke Yorkshire Cancer Research Centenary Professor of Pathology University of Leeds, UK Rapid pace of molecular change Sequencing changes 2012 1,000 genomes
More informationMLH1 Promoter Methylation Frequency in Colorectal Cancer Patients and Related Clinicopathological and Molecular Features
MLH1 Promoter Methylation Frequency in Colorectal Cancer Patients and Related Clinicopathological and Molecular Features Xia Li 1, Xiaoping Yao 1, Yibaina Wang 1, Fulan Hu 1, Fan Wang 1, Liying Jiang 1,
More informationColon cancer: practical molecular diagnostics. Wade S. Samowitz, M.D. University of Utah and ARUP
Colon cancer: practical molecular diagnostics Wade S. Samowitz, M.D. University of Utah and ARUP Disclosure Dr. Samowitz may receive royalties in the future related to the Ventana BRAF V600E antibody.
More informationColorectal cancer (CRC) is one of the most common
Microsatellite Instability in Colorectal Carcinoma The Comparison of Immunohistochemistry and Molecular Biology Suggests a Role for hmlh6 Immunostaining Valérie Rigau, MD; Nicole Sebbagh, BS; Sylviane
More informationMicrosatellite instability profiling of Lynch syndrome-associated cancers Ferreira, Ana Maria Monteiro
University of Groningen Microsatellite instability profiling of Lynch syndrome-associated cancers Ferreira, Ana Maria Monteiro IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's
More information