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|a Brown, Jennifer R.
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|a Massachusetts Institute of Technology. Department of Biology
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|a Regev, Aviv
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|a Hanna, Megan
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|a Tesar, Bethany
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|a Werner, Lillian
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|a Pochet, Nathalie
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|a Asara, John M.
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|a Wang, Yaoyu E.
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|a dal Cin, Paola
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|a Fernandes, Stacey M.
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|a Thompson, Christina
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|a MacConaill, Laura
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|a Wu, Catherine J.
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|a Van de Peer, Yves
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|a Correll, Mick
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|a Regev, Aviv
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|a Neuberg, Donna S.
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|a Freedman, Arnold S.
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|a Integrative Genomic Analysis Implicates Gain of PIK3CA at 3q26 and MYC at 8q24 in Chronic Lymphocytic Leukemia
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|b American Association for Cancer Research,
|c 2014-02-21T18:03:41Z.
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|z Get fulltext
|u http://hdl.handle.net/1721.1/85067
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|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.
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|a Dana-Farber Cancer Institute. Center for Cancer Genome Discovery
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|a Dana-Farber Cancer Institute (Dana-Farber Strategic Plan Initiative)
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|a Dana-Farber Cancer Institute. Center for Cancer Computational Biology
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|a Damon Runyon Cancer Research Foundation (CI-38-07)
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|a Fonds voor Wetenschappelijk Onderzoek--Vlaanderen
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|a Burroughs Wellcome Fund (Career Award at the Scientific Interface)
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|a National Institutes of Health (U.S.) (5PO1-CA120964)
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|a National Institutes of Health (U.S.) (5P30-CA006516)
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|a National Institutes of Health (U.S.) (NIH 5 PO1 CA092625)
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|a National Institutes of Health (U.S.) (K23 CA115682)
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|a National Institutes of Health (U.S.) (Pioneer Award)
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|a Merkin Family Foundation for Stem Cell Research
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|a Howard Hughes Medical Institute
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|a en_US
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|a Article
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|t Clinical Cancer Research
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