Genome Biology

, 11:P37 | Cite as

Diverse somatic mutation patterns and pathway alterations in human cancers

  • Zhengyan Kan
  • Bijay S Jaiswal
  • Somasekar Seshagiri
Poster presentation
  • 1.7k Downloads

Keywords

Prostate Cancer Cancer Type Somatic Mutation Potential Therapeutic Target Cancer Genome 

Systematic characterization of somatic mutations in cancer genomes is essential for understanding the disease and developing targeted therapeutics [1]. Here we report the identification of 2576 somatic mutations across ~1,800 Mb of DNA, representing 1507 coding genes from 441 tumors, consisting of breast, lung, ovarian and prostate cancer types and subtypes. We found that mutation rates and the sets of mutated genes varied substantially across tumor types and subtypes. Statistical analysis identified 77 significantly mutated genes including those encoding protein kinases, G-protein-coupled receptors, such as GRM8, BAI3, AGTRL1 and LPHN3, and other druggable targets. Integrated analysis of somatic mutations and copy number alterations identified a further 35 significantly altered genes including GNAS, suggesting an expanded role for Gα subunits in multiple cancer types. Furthermore, our experimental analyses demonstrate the functional roles of mutant GNAO1 - a Gα subunit, and mutant MAP2K4 - a member of JNK signaling pathway, in oncogenesis. Our study provides an overview of the mutational spectra across major human cancers and identifies several potential therapeutic targets.

References

  1. 1.
    Futreal PA, et al: A census of human cancer genes. Nat Rev Cancer. 2004, 4: 177-183. 10.1038/nrc1299.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Kan et al; licensee BioMed Central Ltd. 2010

This article is published under license to BioMed Central Ltd.

Authors and Affiliations

  • Zhengyan Kan
    • 1
    • 2
  • Bijay S Jaiswal
    • 1
  • Somasekar Seshagiri
    • 1
  1. 1.Department of Molecular BiologyGenentech Inc., 1 DNA WaySouth San FranciscoUSA
  2. 2.Department of BioinformaticsGenentech Inc., 1 DNA WaySouth San FranciscoUSA

Personalised recommendations