The landscape of somatic copy-number alteration across human cancers.

Nature
Authors
Keywords
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.

Year of Publication
2010
Journal
Nature
Volume
463
Issue
7283
Pages
899-905
Date Published
2010 Feb 18
ISSN
1476-4687
URL
DOI
10.1038/nature08822
PubMed ID
20164920
PubMed Central ID
PMC2826709
Links
Grant list
K08CA122833 / CA / NCI NIH HHS / United States
K08 AR055688-03 / AR / NIAMS NIH HHS / United States
R01 GM074024 / GM / NIGMS NIH HHS / United States
P01CA 098101 / CA / NCI NIH HHS / United States
K08 CA122833-02 / CA / NCI NIH HHS / United States
K08 CA134931 / CA / NCI NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
R01CA109038 / CA / NCI NIH HHS / United States
K08 CA122833-01A1 / CA / NCI NIH HHS / United States
R01 CA109038 / CA / NCI NIH HHS / United States
P01 CA085859 / CA / NCI NIH HHS / United States
K08 CA122833 / CA / NCI NIH HHS / United States
P01CA085859 / CA / NCI NIH HHS / United States
P01 CA098101 / CA / NCI NIH HHS / United States
P50CA90578 / CA / NCI NIH HHS / United States
P50 CA090578 / CA / NCI NIH HHS / United States
R01 CA109467 / CA / NCI NIH HHS / United States
Howard Hughes Medical Institute / United States
K08 CA122833-03 / CA / NCI NIH HHS / United States
R01CA109467 / CA / NCI NIH HHS / United States
K08 AR055688-04 / AR / NIAMS NIH HHS / United States
K08 AR055688 / AR / NIAMS NIH HHS / United States
U24 CA126546 / CA / NCI NIH HHS / United States