dc.contributor.author | Brown, Jennifer R. | |
dc.contributor.author | Hanna, Megan | |
dc.contributor.author | Tesar, Bethany | |
dc.contributor.author | Werner, Lillian | |
dc.contributor.author | Pochet, Nathalie | |
dc.contributor.author | Asara, John M. | |
dc.contributor.author | Wang, Yaoyu E. | |
dc.contributor.author | dal Cin, Paola | |
dc.contributor.author | Fernandes, Stacey M. | |
dc.contributor.author | Thompson, Christina | |
dc.contributor.author | MacConaill, Laura | |
dc.contributor.author | Wu, Catherine J. | |
dc.contributor.author | Van de Peer, Yves | |
dc.contributor.author | Correll, Mick | |
dc.contributor.author | Regev, Aviv | |
dc.contributor.author | Neuberg, Donna S. | |
dc.contributor.author | Freedman, Arnold S. | |
dc.date.accessioned | 2014-02-21T18:03:41Z | |
dc.date.available | 2014-02-21T18:03:41Z | |
dc.date.issued | 2012-05 | |
dc.identifier.issn | 1078-0432 | |
dc.identifier.issn | 1557-3265 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/85067 | |
dc.description.abstract | 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. | en_US |
dc.description.sponsorship | Dana-Farber Cancer Institute. Center for Cancer Genome Discovery | en_US |
dc.description.sponsorship | Dana-Farber Cancer Institute (Dana-Farber Strategic Plan Initiative) | en_US |
dc.description.sponsorship | Dana-Farber Cancer Institute. Center for Cancer Computational Biology | en_US |
dc.description.sponsorship | Damon Runyon Cancer Research Foundation (CI-38-07) | en_US |
dc.description.sponsorship | Fonds voor Wetenschappelijk Onderzoek--Vlaanderen | en_US |
dc.description.sponsorship | Burroughs Wellcome Fund (Career Award at the Scientific Interface) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (5PO1-CA120964) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (5P30-CA006516) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (NIH 5 PO1 CA092625) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (K23 CA115682) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Pioneer Award) | en_US |
dc.description.sponsorship | Merkin Family Foundation for Stem Cell Research | en_US |
dc.description.sponsorship | Howard Hughes Medical Institute | en_US |
dc.language.iso | en_US | |
dc.publisher | American Association for Cancer Research | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1158/1078-0432.ccr-11-2342 | en_US |
dc.rights | Creative Commons Attribution-Noncommercial-Share Alike | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | en_US |
dc.source | PMC | en_US |
dc.title | Integrative Genomic Analysis Implicates Gain of PIK3CA at 3q26 and MYC at 8q24 in Chronic Lymphocytic Leukemia | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Brown, J. R., M. Hanna, B. Tesar, L. Werner, N. Pochet, J. M. Asara, Y. E. Wang, et al. “Integrative Genomic Analysis Implicates Gain of PIK3CA at 3q26 and MYC at 8q24 in Chronic Lymphocytic Leukemia.” Clinical Cancer Research 18, no. 14 (July 15, 2012): 3791-3802. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.mitauthor | Regev, Aviv | en_US |
dc.relation.journal | Clinical Cancer Research | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Brown, J. R.; Hanna, M.; Tesar, B.; Werner, L.; Pochet, N.; Asara, J. M.; Wang, Y. E.; dal Cin, P.; Fernandes, S. M.; Thompson, C.; MacConaill, L.; Wu, C. J.; Van de Peer, Y.; Correll, M.; Regev, A.; Neuberg, D.; Freedman, A. S. | en_US |
dc.identifier.orcid | https://orcid.org/0000-0001-8567-2049 | |
mit.license | OPEN_ACCESS_POLICY | en_US |
mit.metadata.status | Complete | |