Improving the Performance of Somatic Mutation Identification by Recovering Circulating Tumor DNA Mutations
Menée notamment à l'aide d'une simulation et d'une cohorte de 93 patientes atteintes d'un cancer métastatique du sein, cette étude française met en évidence l'intérêt d'une nouvelle méthode bio-informatique, utilisant des données de séquençage de l'exome entier d'échantillons tumoraux et d'échantillons de sang total, pour améliorer l'identification systématique de mutations somatiques dans l'ADN tumoral circulant
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 = 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
Cancer Research , résumé, 2015