Integrative Genomic Analysis Implicates Gain of PIK3CA at 3q26 and MYC at 8q24 in Chronic Lymphocytic Leukemia

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...

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Main Authors: Brown, Jennifer R. (Author), Hanna, Megan (Author), Tesar, Bethany (Author), Werner, Lillian (Author), Pochet, Nathalie (Author), Asara, John M. (Author), Wang, Yaoyu E. (Author), dal Cin, Paola (Author), Fernandes, Stacey M. (Author), Thompson, Christina (Author), MacConaill, Laura (Author), Wu, Catherine J. (Author), Van de Peer, Yves (Author), Correll, Mick (Author), Regev, Aviv (Contributor), Neuberg, Donna S. (Author), Freedman, Arnold S. (Author)
Other Authors: Massachusetts Institute of Technology. Department of Biology (Contributor)
Format: Article
Language:English
Published: American Association for Cancer Research, 2014-02-21T18:03:41Z.
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LEADER 03559 am a22005173u 4500
001 85067
042 |a dc 
100 1 0 |a Brown, Jennifer R.  |e author 
100 1 0 |a Massachusetts Institute of Technology. Department of Biology  |e contributor 
100 1 0 |a Regev, Aviv  |e contributor 
700 1 0 |a Hanna, Megan  |e author 
700 1 0 |a Tesar, Bethany  |e author 
700 1 0 |a Werner, Lillian  |e author 
700 1 0 |a Pochet, Nathalie  |e author 
700 1 0 |a Asara, John M.  |e author 
700 1 0 |a Wang, Yaoyu E.  |e author 
700 1 0 |a dal Cin, Paola  |e author 
700 1 0 |a Fernandes, Stacey M.  |e author 
700 1 0 |a Thompson, Christina  |e author 
700 1 0 |a MacConaill, Laura  |e author 
700 1 0 |a Wu, Catherine J.  |e author 
700 1 0 |a Van de Peer, Yves  |e author 
700 1 0 |a Correll, Mick  |e author 
700 1 0 |a Regev, Aviv  |e author 
700 1 0 |a Neuberg, Donna S.  |e author 
700 1 0 |a Freedman, Arnold S.  |e author 
245 0 0 |a Integrative Genomic Analysis Implicates Gain of PIK3CA at 3q26 and MYC at 8q24 in Chronic Lymphocytic Leukemia 
260 |b American Association for Cancer Research,   |c 2014-02-21T18:03:41Z. 
856 |z Get fulltext  |u http://hdl.handle.net/1721.1/85067 
520 |a 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 α subunit in three CLLs carrying PIK3CA amplification. Conclusions: Our findings implicate amplifications of 3q26 focused on PIK3CA and 8q24 focused on MYC in CLL. 
520 |a Dana-Farber Cancer Institute. Center for Cancer Genome Discovery 
520 |a Dana-Farber Cancer Institute (Dana-Farber Strategic Plan Initiative) 
520 |a Dana-Farber Cancer Institute. Center for Cancer Computational Biology 
520 |a Damon Runyon Cancer Research Foundation (CI-38-07) 
520 |a Fonds voor Wetenschappelijk Onderzoek--Vlaanderen 
520 |a Burroughs Wellcome Fund (Career Award at the Scientific Interface) 
520 |a National Institutes of Health (U.S.) (5PO1-CA120964) 
520 |a National Institutes of Health (U.S.) (5P30-CA006516) 
520 |a National Institutes of Health (U.S.) (NIH 5 PO1 CA092625) 
520 |a National Institutes of Health (U.S.) (K23 CA115682) 
520 |a National Institutes of Health (U.S.) (Pioneer Award) 
520 |a Merkin Family Foundation for Stem Cell Research 
520 |a Howard Hughes Medical Institute 
546 |a en_US 
655 7 |a Article 
773 |t Clinical Cancer Research