title: The landscape of somatic copy-number alteration across human cancers.
abstract: A powerful way to discover key genes with causal roles in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here we present high-resolution analyses of somatic copy-number alterations (SCNAs) from 3,131 cancer specimens, belonging largely to 26 histological types. We identify 158 regions of focal SCNA that are altered at significant frequency across several cancer types, of which 122 cannot be explained by the presence of a known cancer target gene located within these regions. Several gene families are enriched among these regions of focal SCNA, including the BCL2 family of apoptosis regulators and the NF-kappaBeta pathway. We show that cancer cells containing amplifications surrounding the MCL1 and BCL2L1 anti-apoptotic genes depend on the expression of these genes for survival. Finally, we demonstrate that a large majority of SCNAs identified in individual cancer types are present in several cancer types.
authors.affiliation: Cancer Program and Medical and Population Genetics Group, The Broad Institute of M.I.T. and Harvard, 7 Cambridge Center.
authors.forename: Rameen
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authors.lastname: Greulich
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authors.lastname: Winckler
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authors.lastname: Fletcher
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authors.lastname: Tabernero
authors.forename: José
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authors.lastname: Baselga
authors.forename: Ming-Sound
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authors.lastname: Tsao
authors.forename: Francesca
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authors.lastname: Demichelis
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authors.lastname: Rubin
authors.forename: Pasi A
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authors.forename: Carmelo
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authors.lastname: Nucera
authors.forename: Ross L
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authors.lastname: Levine
authors.forename: Benjamin L
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authors.lastname: Ebert
authors.forename: Stacey
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authors.lastname: Gabriel
authors.forename: Anil K
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authors.lastname: Rustgi
authors.forename: Cristina R
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authors.lastname: Antonescu
authors.forename: Marc
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authors.lastname: Ladanyi
authors.forename: Anthony
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authors.lastname: Letai
authors.forename: Levi A
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authors.lastname: Garraway
authors.forename: Massimo
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authors.lastname: Loda
authors.forename: David G
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authors.lastname: Beer
authors.forename: Lawrence D
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authors.lastname: True
authors.forename: Aikou
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authors.lastname: Okamoto
authors.forename: Scott L
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authors.lastname: Pomeroy
authors.forename: Samuel
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authors.lastname: Singer
authors.forename: Todd R
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authors.lastname: Golub
authors.forename: Eric S
authors.initials: ES
authors.lastname: Lander
authors.forename: Gad
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authors.lastname: Getz
authors.forename: William R
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authors.lastname: Sellers
authors.forename: Matthew
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authors.lastname: Meyerson
mesh_terms: D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D005784:Gene Amplification / Q000235:genetics; D018628:Gene Dosage / Q000235:genetics*; D023281:Genomics; D006801:Humans; D005810:Multigene Family / Q000235:genetics; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009369:Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D015398:Signal Transduction; D051020:bcl-X Protein / Q000235:genetics
chemical_list: C494811:BCL2L1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein