HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: fj.08-108985v1 22/8/2605    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yeang, C.-H. Articles by Levine, A. Search for Related Content PubMed PubMed Citation Articles by Yeang, C.-H. Articles by Levine, A.

Combinatorial patterns of somatic gene mutations in cancer

Chen-Hsiang Yeang^*,1, Frank McCormick and Arnold Levine^*

^* Simons Center for Systems Biology, Institute for Advanced Study, Princeton, New Jersey, USA; and the

Helen Diller Family Comprehensive Cancer Center and Cancer Research Institute, University of California, San Francisco, California, USA

¹Correspondence: Institute for Advanced Study, 1 Einstein Drive, Princeton, NJ 08540, USA. E-mail: chyeang{at}ias.edu

Cancer is a complex process in which the abnormalities of many genes appear to be involved. The combinatorial patterns of gene mutations may reveal the functional relations between genes and pathways in tumorigenesis as well as identify targets for treatment. We examined the patterns of somatic mutations of cancers from Catalog of Somatic Mutations in Cancer (COSMIC), a large-scale database curated by the Wellcome Trust Sanger Institute. The frequently mutated genes are well-known oncogenes and tumor suppressors that are involved in generic processes of cell-cycle control, signal transduction, and stress responses. These "signatures" of gene mutations are heterogeneous when the cancers from different tissues are compared. Mutations in genes functioning in different pathways can occur in the same cancer (i.e., co-occur), whereas those in genes functioning in the same pathway are rarely mutated in the same sample. This observation supports the view of tumorigenesis as derived from a process like Darwinian evolution. However, certain combinatorial mutational patterns violate these simple rules and demonstrate tissue-specific variations. For instance, mutations of genes in the Ras and Wnt pathways tend to co-occur in the large intestine but are mutually exclusive in cancers of the pancreas. The relationships between mutations in different samples of a cancer can also reveal the temporal orders of mutational events. In addition, the observed mutational patterns suggest candidates of new cosequencing targets that can either reveal novel patterns or validate the predictions deduced from existing patterns. These combinatorial mutational patterns provide guiding information for the ongoing cancer genome projects.—Yeang, C-H., McCormick, F., Levine, A. Combinatorial patterns of somatic gene mutations in cancer.

Key Words: cell cycle control • Ras pathway • Wnt pathway • P53 pathway • Igf • Akt pathway • TGFβ pathway

This article has been cited by other articles:

				P. Pajer, V. Karafiat, V. Pecenka, D. Prukova, J. Dudlova, J. Plachy, P. Kasparova, and M. Dvorak Industasis, a Promotion of Tumor Formation by Nontumorigenic Stray Cells Cancer Res., June 1, 2009; 69(11): 4605 - 4612. [Abstract] [Full Text] [PDF]