Integrated analysis of homozygous deletions, focal amplifications, and sequence alterations in breast and colorectal cancers

Rebecca J. Leary, Jimmy C. Lin, Jordan Cummins, Simina Boca, Laura D. Wood, D. Williams Parsons, Siân Jones, Tobias Sjöblom, Ben Ho Park, Ramon Parsons, Joseph Willis, Dawn Dawson, James K V Willson, Tatiana Nikolskaya, Yuri Nikolsky, Levy Kopelovich, Nick Papadopoulos, Len A. Pennacchio, Tian Li Wang, Sanford D. MarkowitzGiovanni Parmigiani, Kenneth W. Kinzler, Bert Vogelstein, Victor E. Velculescu

Research output: Contribution to journalArticle

221 Scopus citations

Abstract

We have performed a genome-wide analysis of copy number changes in breast and colorectal tumors using approaches that can reliably detect homozygous deletions and amplifications. We found that the number of genes altered by major copy number changes, deletion of all copies or amplification to at least 12 copies per cell, averaged 17 per tumor. We have integrated these data with previous mutation analyses of the Reference Sequence genes in these same tumor types and have identified genes and cellular pathways affected by both copy number changes and point alterations. Pathways enriched for genetic alterations included those controlling cell adhesion, intracellular signaling, DNA topological change, and cell cycle control. These analyses provide an integrated view of copy number and sequencing alterations on a genome-wide scale and identify genes and pathways that could prove useful for cancer diagnosis and therapy.

Original languageEnglish (US)
Pages (from-to)16224-16229
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number42
DOIs
StatePublished - Oct 21 2008

Keywords

  • Amplification
  • Copy number changes
  • Digital Karyotyping
  • High-density SNP arrays
  • Homozygous deletion

ASJC Scopus subject areas

  • General

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    Leary, R. J., Lin, J. C., Cummins, J., Boca, S., Wood, L. D., Parsons, D. W., Jones, S., Sjöblom, T., Park, B. H., Parsons, R., Willis, J., Dawson, D., Willson, J. K. V., Nikolskaya, T., Nikolsky, Y., Kopelovich, L., Papadopoulos, N., Pennacchio, L. A., Wang, T. L., ... Velculescu, V. E. (2008). Integrated analysis of homozygous deletions, focal amplifications, and sequence alterations in breast and colorectal cancers. Proceedings of the National Academy of Sciences of the United States of America, 105(42), 16224-16229. https://doi.org/10.1073/pnas.0808041105