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High-throughput oncogene mutation profiling in human cancer

A Corrigendum to this article was published on 01 April 2007

This article has been updated

Abstract

Systematic efforts are underway to decipher the genetic changes associated with tumor initiation and progression1,2. However, widespread clinical application of this information is hampered by an inability to identify critical genetic events across the spectrum of human tumors with adequate sensitivity and scalability. Here, we have adapted high-throughput genotyping to query 238 known oncogene mutations across 1,000 human tumor samples. This approach established robust mutation distributions spanning 17 cancer types. Of 17 oncogenes analyzed, we found 14 to be mutated at least once, and 298 (30%) samples carried at least one mutation. Moreover, we identified previously unrecognized oncogene mutations in several tumor types and observed an unexpectedly high number of co-occurring mutations. These results offer a new dimension in tumor genetics, where mutations involving multiple cancer genes may be interrogated simultaneously and in 'real time' to guide cancer classification and rational therapeutic intervention.

NOTE: In the version of this article initially published, the name of an author was spelled incorrectly as Laura MacConnaill. The correct spelling is Laura MacConaill. The error has been corrected in the HTML and PDF versions of the article.

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Figure 1: Frequencies of oncogene mutations across human tumor types.
Figure 2: Mutually exclusive and co-occurring oncogene mutations in human cancer.

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  • 14 March 2007

    NOTE: In the version of this article initially published, the name of an author was spelled incorrectly as Laura MacConnaill. The correct spelling is Laura MacConaill. The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank E. Lander and G. Getz for comments and advice. R.K.T. is a Mildred-Scheel fellow of the Deutsche Krebshilfe. R.K.T. is supported by the International Association for the Study of Lung Cancer (IASLC). R.M.D. is supported by the Swiss national science foundation (no: 3100A0-103671/1). A.G and J.M. are supported by the National Cancer Institute through SPORE grant P50CA70907. G.D.D. is supported by the Virginia and Daniel K. Ludwig Trust for Cancer Research, the Quick Family Fund for Cancer Research and the Ronald O. Perelman Fund for Cancer Research at Dana-Farber. I.K.M. and P.S.M. are supported by Accelerate Brain Tumor Cure. I.K.M., L.M.L, T.F.C., and P.S.M. are supported by the Henry E. Singleton Brain Tumor Program. I.K.M., L.M.L, T.F.C., S.F.N., M.M., W.R.S. and P.S.M. are supported by the Brain Tumor Funders' Collaborative. M.M. and L.A.G. are supported by a grant from Genentech, Inc. M.M. is supported by the American Cancer Society. L.A.G is supported by the National Cancer Institute, the Prostate Cancer Foundation, the Burroughs-Wellcome Fund, the Robert Wood Johnson Foundation and the Novartis Institute for Biomedical Research.

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Correspondence to Levi A Garraway.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Distribution of peak height ratios for recurrent oncogene point mutations. (PDF 1731 kb)

Supplementary Fig. 2

Mutation prevalence as determined by high-throughput genotyping. (PDF 666 kb)

Supplementary Fig. 3

Distribution of oncogene mutations by gene. (PDF 1275 kb)

Supplementary Fig. 4

Oncogene mutation prevalence by tumor type. (PDF 2953 kb)

Supplementary Table 1

Oncogene mutations and nucleotide changes. (XLS 120 kb)

Supplementary Table 2

Oncogene mutation peak height ratios. (XLS 75 kb)

Supplementary Table 3

Oncogene mutation assay completion. (XLS 51 kb)

Supplementary Note (PDF 66 kb)

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Thomas, R., Baker, A., DeBiasi, R. et al. High-throughput oncogene mutation profiling in human cancer. Nat Genet 39, 347–351 (2007). https://doi.org/10.1038/ng1975

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