The Landscape of Somatic Copy-Number Alteration Across Human Cancers

Nature. 2010 Feb 18;463(7283):899-905. doi: 10.1038/nature08822.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Survival / genetics
  • DNA Copy Number Variations / genetics*
  • Gene Amplification / genetics
  • Gene Dosage / genetics*
  • Genomics
  • Humans
  • Multigene Family / genetics
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neoplasms / classification
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Signal Transduction
  • bcl-X Protein / genetics

Substances

  • BCL2L1 protein, human
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-X Protein

Associated data

  • GEO/GSE19399