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Systematic investigation of cancer-associated somatic point mutations in SNP databases

Nature Biotechnology volume 31, pages 787–789 (2013)Cite this article

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To the Editor:

Whole-genome and exome sequencing enables the discovery of druggable cancer-driver genes, most commonly through the analysis of somatic point mutations1. As a key step in detecting somatic point mutations, it is common practice to compare sequencing results against public single-nucleotide polymorphism (SNP) databases to help remove previously described variants that occur naturally in the human population. A problem with this approach is that public SNP databases include somatic mutations that may be cancer related, and indiscriminate filtering can often remove such SNPs, even though they may have relevance to disease biology. Here, we carry out a systematic investigation of somatic mutations in SNP databases and illustrate the importance of appropriate filtering. Finally, we propose an improved filtering workflow for the detection of cancer-related mutations.

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Figure 1: Survey of SNP filtering approach and rescued mutations in two example articles.

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Acknowledgements

We thank Y.S. Ju and J.-I. Kim at Wellcome Trust Sanger Institute and Seoul National University for their personal comments regarding this manuscript, and W. Jun and J. Shendure at Beijing Genomics Institute (BGI) and the University of Washington for providing data and comments about data verification. This study was supported by a grant from the National Cancer Center, Republic of Korea (NCC-1110272 and NCC-1310190 to D.H.).

Author contributions D.H. and H.J. conceived of, planned and managed the project, and analyzed sequencing data. J.L. and H.J. developed the genome browser. J.L. assisted in the data analysis. D.H., H.J. and T.B. wrote the manuscript.

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Authors and Affiliations

  1. Division of Convergence Technology, Cancer Genomics Branch, National Cancer Center, Gyeonggi-do, Korea

    HyunChul Jung, Jongkeun Lee & Dongwan Hong

  2. Bioinformatics and Systems Biology Graduate Program, University of California San Diego, La Jolla, California, USA

    HyunChul Jung

  3. College of Natural Sciences, Seoul National University Graduate School, Seoul, Korea

    Thomas Bleazard

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  1. HyunChul Jung
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Correspondence to Dongwan Hong.

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Jung, H., Bleazard, T., Lee, J. et al. Systematic investigation of cancer-associated somatic point mutations in SNP databases. Nat Biotechnol 31, 787–789 (2013). https://doi.org/10.1038/nbt.2681

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