Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9551-6.
Data-driven unbiased curation of the TP53 tumor suppressor gene mutation database and validation by ultradeep sequencing of human tumors.
Edlund K, Larsson O, Ameur A, Bunikis I, Gyllensten U, Leroy B, Sundström M, Micke P, Botling J, Soussi T.
Source
Department of Immunology, and SciLifeLab Uppsala, Uppsala University, SE-751 85 Uppsala, Sweden.Abstract
Cancer
mutation databases are expected to play central roles in personalized
medicine by providing targets for drug development and biomarkers to
tailor treatments to each patient. The accuracy of reported mutations is
a critical issue that is commonly overlooked, which leads to mutation
databases that include a sizable number of spurious mutations, either
sequencing errors or passenger mutations. Here we report an analysis of
the latest version of the TP53 mutation database, including 34,453
mutations. By using several data-driven methods on multiple independent
quality criteria, we obtained a quality score for each report
contributing to the database. This score can now be used to filter for
high-confidence mutations and reports within the database. Sequencing
the entire TP53 gene from various types of cancer using next-generation
sequencing with ultradeep coverage validated our approach for curation.
In summary, 9.7% of all collected studies, mostly comprising numerous
tumors with multiple infrequent TP53 mutations, should be excluded when
analyzing TP53 mutations. Thus, by combining statistical and
experimental analyses, we provide a curated mutation database for TP53
mutations and a framework for mutation database analysis.
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