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dc.contributor.authorWang, Lili
dc.contributor.authorLawrence, Michael S.
dc.contributor.authorWan, Youzhong
dc.contributor.authorStojanov, Petar
dc.contributor.authorSougnez, Carrie
dc.contributor.authorStevenson, Kristen
dc.contributor.authorWerner, Lillian
dc.contributor.authorSivachenko, Andrey
dc.contributor.authorDeLuca, David S.
dc.contributor.authorZhang, Li
dc.contributor.authorZhang, Wandi
dc.contributor.authorVartanov, Alexander R.
dc.contributor.authorFernandes, Stacey M.
dc.contributor.authorGoldstein, Natalie R.
dc.contributor.authorFolco, Eric G.
dc.contributor.authorCibulskis, Kristian
dc.contributor.authorTesar, Bethany
dc.contributor.authorSievers, Quinlan L.
dc.contributor.authorShefler, Erica
dc.contributor.authorGabriel, Stacey B.
dc.contributor.authorHacohen, Nir
dc.contributor.authorReed, Robin
dc.contributor.authorMeyerson, Matthew L.
dc.contributor.authorGolub, Todd R.
dc.contributor.authorNeuberg, Donna S.
dc.contributor.authorBrown, Jennifer R.
dc.contributor.authorGetz, Gad
dc.contributor.authorWu, Catherine J.
dc.contributor.authorLander, Eric S.
dc.contributor.authorLander, Eric Steven
dc.date.accessioned2014-02-03T20:27:29Z
dc.date.available2014-02-03T20:27:29Z
dc.date.issued2011-12
dc.identifier.issn0028-4793
dc.identifier.issn1533-4406
dc.identifier.urihttp://hdl.handle.net/1721.1/84659
dc.description.abstractBackground: The somatic genetic basis of chronic lymphocytic leukemia, a common and clinically heterogeneous leukemia occurring in adults, remains poorly understood. Methods: We obtained DNA samples from leukemia cells in 91 patients with chronic lymphocytic leukemia and performed massively parallel sequencing of 88 whole exomes and whole genomes, together with sequencing of matched germline DNA, to characterize the spectrum of somatic mutations in this disease. Results: Nine genes that are mutated at significant frequencies were identified, including four with established roles in chronic lymphocytic leukemia (TP53 in 15% of patients, ATM in 9%, MYD88 in 10%, and NOTCH1 in 4%) and five with unestablished roles (SF3B1, ZMYM3, MAPK1, FBXW7, and DDX3X). SF3B1, which functions at the catalytic core of the spliceosome, was the second most frequently mutated gene (with mutations occurring in 15% of patients). SF3B1 mutations occurred primarily in tumors with deletions in chromosome 11q, which are associated with a poor prognosis in patients with chronic lymphocytic leukemia. We further discovered that tumor samples with mutations in SF3B1 had alterations in pre–messenger RNA (mRNA) splicing. Conclusions: Our study defines the landscape of somatic mutations in chronic lymphocytic leukemia and highlights pre-mRNA splicing as a critical cellular process contributing to chronic lymphocytic leukemia.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.). National Human Genome Research Institute (Grant U54HG003067)en_US
dc.description.sponsorshipNational Cancer Institute (U.S.) (Grant 5R21CA115043-2)en_US
dc.language.isoen_US
dc.publisherNew England Journal of Medicineen_US
dc.relation.isversionofhttp://dx.doi.org/10.1056/NEJMoa1109016en_US
dc.rightsCreative Commons Attribution-Noncommercial-Share Alike 3.0en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/en_US
dc.sourcePMCen_US
dc.titleSF3B1 and Other Novel Cancer Genes in Chronic Lymphocytic Leukemiaen_US
dc.typeArticleen_US
dc.identifier.citationWang, Lili, Michael S. Lawrence, Youzhong Wan, Petar Stojanov, Carrie Sougnez, Kristen Stevenson, Lillian Werner, et al. “SF3B1 and Other Novel Cancer Genes in Chronic Lymphocytic Leukemia.” New England Journal of Medicine 365, no. 26 (December 29, 2011): 2497-2506.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.mitauthorLander, Eric S.en_US
dc.relation.journalNew England Journal of Medicineen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsWang, Lili; Lawrence, Michael S.; Wan, Youzhong; Stojanov, Petar; Sougnez, Carrie; Stevenson, Kristen; Werner, Lillian; Sivachenko, Andrey; DeLuca, David S.; Zhang, Li; Zhang, Wandi; Vartanov, Alexander R.; Fernandes, Stacey M.; Goldstein, Natalie R.; Folco, Eric G.; Cibulskis, Kristian; Tesar, Bethany; Sievers, Quinlan L.; Shefler, Erica; Gabriel, Stacey; Hacohen, Nir; Reed, Robin; Meyerson, Matthew; Golub, Todd R.; Lander, Eric S.; Neuberg, Donna; Brown, Jennifer R.; Getz, Gad; Wu, Catherine J.en_US
mit.licenseOPEN_ACCESS_POLICYen_US
mit.metadata.statusComplete


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