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Molecular Cancer

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Open Access 01-12-2011 | Research

The structural impact of cancer-associated missense mutations in oncogenes and tumor suppressors

Authors: Henning Stehr, Seon-Hi J Jang, José M Duarte, Christoph Wierling, Hans Lehrach, Michael Lappe, Bodo MH Lange

Published in: Molecular Cancer | Issue 1/2011

Abstract

Background

Current large-scale cancer sequencing projects have identified large numbers of somatic mutations covering an increasing number of different cancer tissues and patients. However, the characterization of these mutations at the structural and functional level remains a challenge.

Results

We present results from an analysis of the structural impact of frequent missense cancer mutations using an automated method. We find that inactivation of tumor suppressors in cancer correlates frequently with destabilizing mutations preferably in the core of the protein, while enhanced activity of oncogenes is often linked to specific mutations at functional sites. Furthermore, our results show that this alteration of oncogenic activity is often associated with mutations at ATP or GTP binding sites.

Conclusions

With our findings we can confirm and statistically validate the hypotheses for the gain-of-function and loss-of-function mechanisms of oncogenes and tumor suppressors, respectively. We show that the distinct mutational patterns can potentially be used to pre-classify newly identified cancer-associated genes with yet unknown function.

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Title: The structural impact of cancer-associated missense mutations in oncogenes and tumor suppressors
Authors: Henning Stehr
Seon-Hi J Jang
José M Duarte
Christoph Wierling
Hans Lehrach
Michael Lappe
Bodo MH Lange
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: Molecular Cancer / Issue 1/2011
Electronic ISSN: 1476-4598
DOI: https://doi.org/10.1186/1476-4598-10-54

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