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dc.contributor.authorLander, Eric S.
dc.contributor.authorDrier, Yotam
dc.contributor.authorLawrence, Michael S.
dc.contributor.authorCarter, Scott L.
dc.contributor.authorStewart, Chip
dc.contributor.authorGabriel, Stacey B.
dc.contributor.authorMeyerson, Matthew L.
dc.contributor.authorBeroukhim, Rameen
dc.contributor.authorGetz, Gad
dc.date.accessioned2013-09-18T14:19:06Z
dc.date.available2013-09-18T14:19:06Z
dc.date.issued2012-11
dc.date.submitted2012-10
dc.identifier.issn1088-9051
dc.identifier.urihttp://hdl.handle.net/1721.1/80787
dc.description.abstractWhole-genome sequencing using massively parallel sequencing technologies enables accurate detection of somatic rearrangements in cancer. Pinpointing large numbers of rearrangement breakpoints to base-pair resolution allows analysis of rearrangement microhomology and genomic location for every sample. Here we analyze 95 tumor genome sequences from breast, head and neck, colorectal, and prostate carcinomas, and from melanoma, multiple myeloma, and chronic lymphocytic leukemia. We discover three genomic factors that are significantly correlated with the distribution of rearrangements: replication time, transcription rate, and GC content. The correlation is complex, and different patterns are observed between tumor types, within tumor types, and even between different types of rearrangements. Mutations in the APC gene correlate with and, hence, potentially contribute to DNA breakage in late-replicating, low %GC, untranscribed regions of the genome. We show that somatic rearrangements display less microhomology than germline rearrangements, and that breakpoint loci are correlated with local hypermutability with a particular enrichment for C ↔ G transversions.en_US
dc.language.isoen_US
dc.publisherCold Spring Harbor Laboratory Pressen_US
dc.relation.isversionofhttp://dx.doi.org/10.1101/gr.141382.112en_US
dc.rightsCreative Commons Attributionen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/en_US
dc.sourceGenome Researchen_US
dc.titleSomatic rearrangements across cancer reveal classes of samples with distinct patterns of DNA breakage and rearrangement-induced hypermutabilityen_US
dc.typeArticleen_US
dc.identifier.citationDrier, Y., M. S. Lawrence, S. L. Carter, C. Stewart, S. B. Gabriel, E. S. Lander, M. Meyerson, R. Beroukhim, and G. Getz. “Somatic rearrangements across cancer reveal classes of samples with distinct patterns of DNA breakage and rearrangement-induced hypermutability.” Genome Research 23, no. 2 (February 1, 2013): 228-235.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.mitauthorLander, Eric S.en_US
dc.relation.journalGenome Researchen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsDrier, Y.; Lawrence, M. S.; Carter, S. L.; Stewart, C.; Gabriel, S. B.; Lander, E. S.; Meyerson, M.; Beroukhim, R.; Getz, G.en_US
mit.licensePUBLISHER_CCen_US


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