title: Profiling of actionable gene alterations in ovarian cancer by targeted deep sequencing.
abstract: To construct a profile of therapeutically actionable gene alterations in the major histological types of ovarian cancer, 72 Japanese patients with surgically resected ovarian cancers were selected from an original cohort consisting of 267 patients who had not received pre-treatment before surgery. Somatic mutations and copy number alterations at 740 hotspots in 46 cancer-related genes were detected by deep sequencing of genomic DNAs obtained from snap-frozen tumor tissues using a next generation sequencer. The alterations were verified by Sanger sequencing and quantitative genomic PCR. Mutations and/or copy number aberrations which will make tumors respond to molecular targeting drugs were detected in nine genes of 35/72 (48.6%) patients; PIK3CA (25.0%), KRAS (13.9%), ERBB2 (4.3%), PTEN (2.8%), RB1 (2.8%), CDKN2A (2.8%), AKT1 (1.4%), CTNNB1 (1.4%) and NRAS (1.4%). These mutations tended to occur in a mutually exclusive manner. Non-serous histological type tumors showed such actionable gene alterations frequently (32/47; 68.1%). Therefore, ovarian cancers, particularly of non-serous types, frequently carry gene aberrations that link to therapy using molecular targeting drugs.
authors.affiliation: Division of Genome Biology, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Takenaka
authors.affiliation: Division of Genome Biology, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors.forename: Motonobu
authors.initials: M
authors.lastname: Saito
authors.affiliation: Division of Genome Biology, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors.forename: Reika
authors.initials: R
authors.lastname: Iwakawa
authors.affiliation: Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo 105-8471, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Yanaihara
authors.affiliation: Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo 105-8471, Japan.
authors.forename: Misato
authors.initials: M
authors.lastname: Saito
authors.affiliation: Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Kato
authors.affiliation: Division of Genetics, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ichikawa
authors.affiliation: Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Shibata
authors.affiliation: Division of Genome Biology, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Yokota
authors.affiliation: Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo 105-8471, Japan.
authors.forename: Aikou
authors.initials: A
authors.lastname: Okamoto
authors.affiliation: Division of Genome Biology, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kohno
mesh_terms: D045744:Cell Line, Tumor; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D017422:Sequence Analysis, DNA / Q000379:methods*