title: Improving the Performance of Somatic Mutation Identification by Recovering Circulating Tumor DNA Mutations.
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 = 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 Res; 76(20); 5954-61. ©2016 AACR.
authors.affiliation: INSERM Unit U981, Gustave Roussy, Villejuif, France. Faculté de Médecine, Kremlin-Bicêtre, Université Paris Sud, France.
authors.forename: Yu
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Medical Biology and Pathology, Translational Research Laboratory and BioBank, Gustave Roussy, Villejuif, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Jovelet
authors.affiliation: Biostatistics Department, Institut Claudius Regaud, IUCT-Oncopole, Toulouse, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Filleron
authors.affiliation: INSERM Unit U981, Gustave Roussy, Villejuif, France. Drug Development Department (DITEP), Gustave Roussy, Villejuif, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Pedrero
authors.affiliation: Department of Medical Biology and Pathology, Translational Research Laboratory and BioBank, Gustave Roussy, Villejuif, France.
authors.forename: Nelly
authors.initials: N
authors.lastname: Motté
authors.affiliation: Bioinformatics Core Facility, Gustave Roussy, Villejuif, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Boursin
authors.affiliation: Bioinformatics Core Facility, Gustave Roussy, Villejuif, France.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Medical Oncology, Gustave Roussy, Villejuif, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Massard
authors.affiliation: Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Nantes, France.
authors.forename: Mario
authors.initials: M
authors.lastname: Campone
authors.affiliation: Department of Medical Oncology, Centre François Baclesse, Caen, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Levy
authors.affiliation: Department of Medical Oncology, Institut Curie, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Diéras
authors.affiliation: Department of Medical Oncology, Centre Léon Bérard, Inserm U1052, Lyon, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachelot
authors.affiliation: R&D, UNICANCER, Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Garrabey
authors.affiliation: INSERM Unit U981, Gustave Roussy, Villejuif, France. Faculté de Médecine, Kremlin-Bicêtre, Université Paris Sud, France. Drug Development Department (DITEP), Gustave Roussy, Villejuif, France. Department of Medical Oncology, Gustave Roussy, Villejuif, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
authors.affiliation: INSERM Unit U981, Gustave Roussy, Villejuif, France. Department of Medical Biology and Pathology, Translational Research Laboratory and BioBank, Gustave Roussy, Villejuif, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Lacroix
authors.affiliation: INSERM Unit U981, Gustave Roussy, Villejuif, France. Faculté de Médecine, Kremlin-Bicêtre, Université Paris Sud, France. Department of Medical Oncology, Gustave Roussy, Villejuif, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: André
authors.affiliation: INSERM Unit U981, Gustave Roussy, Villejuif, France. celine.lefebvre@gustaveroussy.fr.
authors.forename: Celine
authors.initials: C
authors.lastname: Lefebvre
mesh_terms: D019985:Benchmarking; D001943:Breast Neoplasms / Q000235:genetics*; D058534:Class I Phosphatidylinositol 3-Kinases; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics*; D059472:Exome; D005260:Female; D016158:Genes, p53; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human