title: Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples.
abstract: Detection of somatic point substitutions is a key step in characterizing the cancer genome. However, existing methods typically miss low-allelic-fraction mutations that occur in only a subset of the sequenced cells owing to either tumor heterogeneity or contamination by normal cells. Here we present MuTect, a method that applies a Bayesian classifier to detect somatic mutations with very low allele fractions, requiring only a few supporting reads, followed by carefully tuned filters that ensure high specificity. We also describe benchmarking approaches that use real, rather than simulated, sequencing data to evaluate the sensitivity and specificity as a function of sequencing depth, base quality and allelic fraction. Compared with other methods, MuTect has higher sensitivity with similar specificity, especially for mutations with allelic fractions as low as 0.1 and below, making MuTect particularly useful for studying cancer subclones and their evolution in standard exome and genome sequencing data.
authors: The Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. gadgetz@broadinstitute.org
authors: Kristian
authors: K
authors: Cibulskis
authors: Michael S
authors: MS
authors: Lawrence
authors: Scott L
authors: SL
authors: Carter
authors: Andrey
authors: A
authors: Sivachenko
authors: David
authors: D
authors: Jaffe
authors: Carrie
authors: C
authors: Sougnez
authors: Stacey
authors: S
authors: Gabriel
authors: Matthew
authors: M
authors: Meyerson
authors: Eric S
authors: ES
authors: Lander
authors: Gad
authors: G
authors: Getz
mesh_terms: D001499:Bayes Theorem; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics*; D015894:Genome, Human; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D017354:Point Mutation; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D004273:DNA, Neoplasm
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