The landscape of somatic copy-number alteration across human cancers

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 histologica...

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Published in:Nature (London) 2010-02, Vol.463 (7283), p.899-905
Main Authors: Yecies, Derek, Gabriel, Stacey, Porter, Dale, Nucera, Carmelo, Antonescu, Cristina R, Chiang, Derek Y, Janne, Pasi A, Greulich, Heidi, Loo, Alice, Prensner, John, Maher, Elizabeth, Rustgi, Anil K, Ligon, Azra H, Tanaka, Kumiko E, Kaye, Frederic J, Ebert, Benjamin L, Pomeroy, Scott L, Lander, Eric S, Fletcher, Jonathan A, Okamoto, Aikou, Signoretti, Sabina, Haery, Leila, Reich, Michael, Dobson, Jennifer, Raychaudhuri, Soumya, Wei, Guo, Baselga, José, Tsao, Ming-Sound, Letai, Anthony, Getz, Gad, Liefeld, Ted, Donovan, Jerry, Levine, Ross L, Beer, David G, Daly, Mark J, Sasaki, Hidefumi, Pinchback, Reid M, Bass, Adam J, Hoffman, Carter, Ladanyi, Marc, True, Lawrence D, Cho, Yoon-Jae, Sellers, William R, Tabernero, Josep, Demichelis, Francesca, Tepper, Joel E, Golub, Todd R, Meyerson, Matthew, Boehm, Jesse S, Mermel, Craig H, Loda, Massimo, Weir, Barbara A, Beroukhim, Rameen, Singer, Samuel, Urashima, Mitsuyoshi, Gao, Qing, Lawrence, Michael S, Rubin, Mark A, Barretina, Jordi, Garraway, Levi A, Winckler, Wendy, Mc Henry, Kevin T
Format: Article
Language:English
Subjects:
Apoptosis - genetics
bcl-X Protein - genetics
Biological and medical sciences
Cancer
Carcinogenesis
Carcinogenesis, carcinogens and anticarcinogens
Cell Line, Tumor
Cell Survival - genetics
DNA Copy Number Variations - genetics
Gene Amplification - genetics
Gene Dosage - genetics
General aspects
Genes
Genetic aspects
Genetic variation
Genetics
Genomics
Health aspects
Humans
Medical sciences
Multigene Family - genetics
Myeloid Cell Leukemia Sequence 1 Protein
Neoplasms - classification
Neoplasms - genetics
Neoplasms - pathology
Proto-Oncogene Proteins c-bcl-2 - genetics
Risk factors
Signal Transduction
Tumors
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Summary: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.
ISSN:0028-0836
1476-4687
DOI:10.1038/nature08822