Improving the Performance of Somatic Mutation Identification by Recovering Circulating Tumor DNA Mutations - Archive ouverte HAL Access content directly
Journal Articles Cancer Research Year : 2016

Improving the Performance of Somatic Mutation Identification by Recovering Circulating Tumor DNA Mutations

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Thomas Filleron

Abstract

DNA extracted from cancer patients' whole blood may contain somatic mutations from circulating tumor DNA (ctDNA) fragments. In this study, we introduce cmDetect, a computational method for the systematic identification of ctDNA mutations using whole-exome sequencing of a cohort of tumor and corresponding peripheral whole-blood samples. Through the analysis of simulated data, we demonstrated an increase in sensitivity in calling somatic mutations by combining cmDetect to two widely used mutation callers. In a cohort of 93 breast cancer metastatic patients, cmDetect identified ctDNA mutations in 54% of the patients and recovered somatic mutations in cancer genes EGFR, PIK3CA, and TP53. We further showed that cmDetect detected ctDNA in 89% of patients with confirmed mutated cell–free tumor DNA by plasma analyses (n ¼ 9) within 46 pan-cancer patients. Our results prompt immediate consideration of the use of this method as an additional step in somatic mutation calling using whole-exome sequencing data with blood samples as controls .
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Dates and versions

inserm-01377103 , version 1 (06-10-2016)

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Yu Fu, Cécile Jovelet, Thomas Filleron, Marion Pedrero, Nelly Motté, et al.. Improving the Performance of Somatic Mutation Identification by Recovering Circulating Tumor DNA Mutations. Cancer Research, 2016, 76, Epub ahead of print. ⟨10.1158/0008-5472.CAN-15-3457⟩. ⟨inserm-01377103⟩
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