The landscape of somatic copy-number alteration across human cancers

Nature 463, 899-905(18 February 2010). Published: 2010.02.17

Rameen Beroukhim*, Craig H. Mermel*, Dale Porter, Guo Wei, Soumya Raychaudhuri, Jerry Donovan, Jordi Barretina, Jesse S. Boehm, Jennifer Dobson, Mitsuyoshi Urashima, Kevin T. Mc Henry, Reid M. Pinchback, Azra H. Ligon, Yoon-Jae Cho, Leila Haery, Heidi Greulich, Michael Reich, Wendy Winckler, Michael S. Lawrence, Barbara A. Weir, Kumiko E. Tanaka, Derek Y. Chiang, Adam J. Bass, Alice Loo, Carter Hoffman, John Prensner, Ted Liefeld, Qing Gao, Derek Yecies, Sabina Signoretti, Elizabeth Maher, Frederic J. Kaye, Hidefumi Sasaki, Joel E. Tepper, Jonathan A. Fletcher, Josep Tabernero, Jose Baselga, Ming-Sound Tsao, Francesca DeMichelis, Mark A. Rubin, Pasi A. Janne, Mark J. Daly, Carmelo Nucera, Ross L. Levine, Benjamin L. Ebert, Stacey Gabriel, Anil K. Rustgi, Cristina R. Antonescu, Marc Ladanyi, Anthony Letai, Levi A. Garraway, Massimo Loda, David G. Beer, Lawrence D. True, Aikou Okamoto, Scott L. Pomeroy, Samuel Singer, Todd R. Golub, Eric S. Lander1, Gad Getz, William R. Sellers & Matthew Meyerson

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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-???? 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.

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Supplemental Data

Description Link/Filename
Supplementary information contents http://www.nature.com/nature/journal/v463/n7283/suppinfo/nature08822.html
Supplementary Figures and Text http://www.nature.com/nature/journal/v463/n7283/extref/Nature08822-s1.pdf
Supplementary Table 1 http://www.nature.com/nature/journal/v463/n7283/extref/Nature08822-s2.xls
Supplementary Table 2 http://www.nature.com/nature/journal/v463/n7283/extref/Nature08822-s3.xls
Supplementary Table 3 http://www.nature.com/nature/journal/v463/n7283/extref/Nature08822-s4.xls
Supplementary Table 4 http://www.nature.com/nature/journal/v463/n7283/extref/Nature08822-s5.xls
Supplementary Table 5 http://www.nature.com/nature/journal/v463/n7283/extref/Nature08822-s6.xls
Supplementary Table 6 http://www.nature.com/nature/journal/v463/n7283/extref/Nature08822-s7.xls
Supplementary Table 7 http://www.nature.com/nature/journal/v463/n7283/extref/Nature08822-s8.xls
Supplementary Table 8 http://www.nature.com/nature/journal/v463/n7283/extref/Nature08822-s9.xls