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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Integrative genomic analysis implicates gain of PIK3CA at 3q26 and MYC at 8q24 in chronic lymphocytic leukemia
Clinical Cancer Research, Volume 18, No. 14, Year 2012
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Description
Purpose: The disease course of chronic lymphocytic leukemia (CLL) varies significantly within cytogenetic groups. We hypothesized that high-resolution genomic analysis of CLL would identify additional recurrent abnormalities associated with short time-to-first therapy (TTFT). Experimental Design: We undertook high-resolution genomic analysis of 161 prospectively enrolled CLLs using Affymetrix 6.0 SNP arrays, and integrated analysis of this data set with gene expression profiles. Results: Copy number analysis (CNA) of nonprogressive CLL reveals a stable genotype, with a median of only 1 somatic CNA per sample. Progressive CLL with 13q deletion was associated with additional somatic CNAs, and a greater number of CNAs was predictive of TTFT. We identified other recurrent CNAs associated with short TTFT: 8q24 amplification focused on the cancer susceptibility locus near MYC in 3.7%; 3q26 amplifications focused on PIK3CA in 5.6%; and 8p deletions in 5% of patients. Sequencing of MYC further identified somatic mutations in two CLLs. We determined which catalytic subunits of phosphoinositide 3-kinase (PI3K) were in active complex with the p85 regulatory subunit and showed enrichment for the a subunit in three CLLs carrying PIK3CA amplification. Conclusions: Our findings implicate amplifications of 3q26 focused on PIK3CA and 8q24 focused on MYC in CLL. ©2012 AACR.
Authors & Co-Authors
Brown, Jennifer R.
United States, Boston
Dana-farber Cancer Institute
United States, Boston
Harvard Medical School
Pochet, Nathalie L.M.M.
United States, Cambridge
Broad Institute
Belgium, Ghent
Vlaams Instituut Voor Biotechnologie
Dal Cin, Paola S.
United States, Boston
Brigham and Women's Hospital
MacConaill, Laura E.
United States, Boston
Dana-farber Cancer Institute
United States, Boston
Brigham and Women's Hospital
Van de Peer, Y.
Belgium, Ghent
Vlaams Instituut Voor Biotechnologie
Regev, Aviv
United States, Cambridge
Broad Institute
United States, Chevy Chase
Howard Hughes Medical Institute
Neuberg, Donna S.
United States, Boston
Dana-farber Cancer Institute
Statistics
Citations: 75
Authors: 7
Affiliations: 7
Identifiers
Doi:
10.1158/1078-0432.CCR-11-2342
ISSN:
15573265
Research Areas
Cancer
Genetics And Genomics