Cited by 251Cancer Genomics and DiagnosticsChromatin Remodeling and CancerBioinformatics and Genomic Networks

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Combinatorial patterns of somatic gene mutations in cancer

Yeang, Chen-Hsiang, McCormick, Frank, Levine, Arnold·2008·The FASEB Journal

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Abstract

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. FASEB J. 22, 2605–2622 (2008)

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Authors: Yeang, C.-H., McCormick, F., & Levine, A.
Affiliations: Institute for Advanced Study (US)
University of California, San Francisco (US)
ORCID: Yeang, Chen-Hsiang
McCormick, Frank
Levine, Arnold
Venue: The FASEB Journal
Publisher: Wiley
Published: 2008-04-23
Volume: 22
Issue: 8
Pages: 2605-2622
ISSN: 0892-6638 (ISSN-L)
1530-6860
DOI: 10.1096/fj.08-108985
OpenAlex: W2126172213
Cited by: 251
References: 54
Citations by year: 2026: 2 · 2025: 2 · 2024: 11 · 2023: 9 · 2022: 13 · 2021: 14 · 2020: 15 · 2019: 23 · 2018: 15 · 2017: 18 · 2016: 22 · 2015: 24 · 2014: 23 · 2013: 9 · 2012: 11
FWCI: 0.96
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: The FASEB Journal (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
Keywords: somatic mutations, COSMIC, oncogenes, tumor suppressor, co-occurring mutations, pathway signatures, Ras signaling, Wnt signaling
MeSH terms: Cell Cycle, Humans, Models, Genetic, Mutation, Neoplasms, Oncogenes, Organ Specificity, Stress, Physiological, Signal Transduction, Genes, Tumor Suppressor, Databases, Genetic, Cell Line, Tumor

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Combinatorial patterns of somatic gene mutations in cancer

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