CGC myeloid malignancy working group updates. Xinjie Xu & Rashmi Kanagal-Shamanna
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1 CGC myeloid malignancy working group updates Xinjie Xu & Rashmi Kanagal-Shamanna
2 Group members Gordana Raca Children's Hospital Los Angeles Xinjie Xu University of Utah ARUP Laboratories Rashmi Kanagal-Shamanna M.D. Anderson Cancer Center Amanda Dixon-Mciver IGENZ, AUCK, NZ Anwar Iqbal University of Rochester Ashwini Yenamandra Vanderbilt Univ Medical Center
3 Group members Patty Greipp Mayo Clinic Christine Bryke Beth Israel Deaconess Medical Center Marilyn Slovak Contract work Jennelle Hodge Cedars-Sinai Medical Center Emma Huxley Sally Jeffries Birmingham Laboratory in England
4 Group members Patrick Alan Lennon PathGroup Min Fang University of Washington Shashi Shetty Case Western Reserve University Fabiola Quintero-Rivera UCLA
5 Goals Publish 3 review papers to discuss the clinical utility of genomic copy number abnormalities and copy neutral LOH detection in AML MDS MPN and MDS/MPN Support the Compendium of Cancer Genome Aberrations
6 Efforts 1. Discussions on 9 hourly conference calls since August 2015 Reviewed close to 100 articles
7 Accomplishments Compiled 2 summary tables using extracted data Results from literature review Relevant loci
8 Table 1: Literature Review
9 Data Extracted for Literature Review
10 Data extracted for Relevant Loci
11 Key findings AML MDS MPN MDS/MPN
12 DIAG 7q (secondary AML) Important Loci in AML COPY NUMBER LOSS (DELETIONS) 7q (CUX), 17p (TP53) RECURRENT 3p14.1 (FHIT), 3p13 (FOXP1), 3q11.2, 3q26.1, 4q24 (TET2), 5q, 6p22, 6p25, 6q27 (RPS6KA2), 9p (CDKN2A), 9q, 10q, 11p (WT1), 11q, 12p (ETV6, CDKN1B), 16q, 17q11.2 (NF1), 17q11.2 (SUZ12), 18p, 20q, Xp11.4 (BCOR), Xq25 (STAG2) DIAG 4q (associated with CBF AML) COPY NUMBER GAIN (DUPLICATIONS) 8q24 amplification (MYC) RECURRENT 1p, 6p21.1, chr 8, 8q24 gain and amplification (MYC), 11q, 13q, 20q, 21q, 22q DIAG COPY NEUTRAL LOSS OF HETEROZYGOSITY (CN-LOH) 9p (JAK2) secondary AML h/o MPN 7q (EZH2), 13q (FLT3 mutations), 17p (TP53), 21q (RUNX1 mutation) RECURRENT 1p, 2p/2q, 3 (terminal), 4q24 (TET2), 5q, 6p21-6pter, 6pter-6p12, 11q, 12p, 19q13 (CEBPA mutations) 13q (FLT3 inhibitors)
13 Recurrent loci of CNLOH in AML Higher rate of disease recurrence Prognostic significance of 13q (FLT3) Gronseth CM and Fang M et al. Cancer Sep 1;121(17): Prognostic significance of acquired copy-neutral loss of heterozygosity in acute myeloid leukemia.
14 Important Loci in MDS DIAG RECURRENT COPY NUMBER LOSS (DELETIONS) 5q (RPS14), 11q, 12p, 20q, Monosomy Y, 3q, and inv 3/t(3q), 7q22 (CUX1), 7q31, 7q34 1p21.3 (MPL), 6q13 DIAG 10q26.3 (ADAM), 17q (iso) COPY NUMBER GAIN (DUPLICATIONS) RECURRENT Trisomy 8, 8q24 (MYC), 21q11.2, Trisomy 21 DIAG RECURRENT COPY NEUTRAL LOSS OF HETEROZYGOSITY (CN-LOH) 21q11.2-qter (RUNX1) 1p, 1p21.3 (MPL), 4q (TET), 9p (JAK2), 11q (CBL), 13q (FLT3), 14q
15 CUX1 Nature Genetics 46, (2014) Blood :
16 Important Loci in MDS/MPN COPY NUMBER LOSS (DELETIONS) DIAG RECURRENT Co-deletion of ETV6 and AEBP2 associated with leukemic transformation 1p21.3 (MPL), 4q24 (TET2), del(5)(q13-q33), 6p (JARID2), 6q, 7q22.2 (CUX1), 7q34, 7q36.1 (EZH2), 9q, 10q21.1, 11q14.1, 11p15.4-p15.5, 12p (ETV6, AEBP2), del13q14-q22, 17p13.1 (TP53), 17q (SUZ12), 20q11.2-q12, 20q13.12 COPY NUMBER GAIN (DUPLICATIONS) DIAG RECURRENT 1q, 8p12, 8, 9q, 11, 12p, 13q22.3, 16p13.3, 21p11.2-q11.2, 21q22 DIAG 9p (JAK2) COPY NEUTRAL LOSS OF HETEROZYGOSITY (CN-LOH) 9p (JAK2) associated with disease progression RECURRENT 1p21.3 (MPL), 4q24 (TET2), 4q24-4q35, 7q32.1-7q36.3, 9p, 11q q25 (CBL), 13 (FLT3), 14q, 17, 19p, 21 9p (JAK2 inhibitors), 13 (FLT3 inhibitors)
17 Important Loci in MPN COPY NUMBER LOSS (DELETIONS) DIAG RECURRENT 17p (TP53), 5q, 6p (JARID2), 7q (EZH2), 12p (ETV6, AEBP2), 17q (SUZ12) - associated with leukemic transformation COPY NUMBER GAIN (DUPLICATIONS) DIAG RECURRENT 9p (JAK2, PV to post PV MF) 1q, 3q COPY NEUTRAL LOSS OF HETEROZYGOSITY (CN-LOH) DIAG RECURRENT 1p (MPL, ET to post ET MF), 9p (JAK2, PV to post PV MF), 17p (TP53, associated with leukemia transformation)
18
19 Efforts supporting CCGA Contributed 6 pages so far AML/MDS with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) AML with NPM1 mutation AML with t(6;9)(p23;q34); DEK-NUP214 AML (megakaryoblastic) with t(1;22)(p13;q13); RBM15- MKL1 AML with t(8;21)(q22;22); RUNX1-RUNX1T1 AML with CUX1 deletion Make our data available to the compendium after publication
20 Goals for next year Publication of review papers 3 sub-groups Continue supporting the compendium
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