title: Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status.
abstract: We evaluated homologous recombination deficient (HRD) phenotypes in epithelial ovarian cancer (EOC) considering BRCA1, BRCA2, and RAD51C in a large well-annotated patient set. We evaluated EOC patients for germline deleterious mutations (n = 899), somatic mutations (n = 279) and epigenetic alterations (n = 482) in these genes using NGS and genome-wide methylation arrays. Deleterious germline mutations were identified in 32 (3.6%) patients for BRCA1, in 28 (3.1%) for BRCA2 and in 26 (2.9%) for RAD51C. Ten somatically sequenced patients had deleterious alterations, six (2.1%) in BRCA1 and four (1.4%) in BRCA2. Fifty two patients (10.8%) had methylated BRCA1 or RAD51C. HRD patients with germline or somatic alterations in any gene were more likely to be high grade serous, have an earlier diagnosis age and have ovarian and/or breast cancer family history. The HRD phenotype was most common in high grade serous EOC. Identification of EOC patients with an HRD phenotype may help tailor specific therapies.
authors: Department of Laboratory Medicine and Pathology, Division of Experimental Pathology, Mayo Clinic, Rochester, Minnesota.
authors: J M
authors: JM
authors: Cunningham
authors: Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota.
authors: M S
authors: MS
authors: Cicek
authors: Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
authors: N B
authors: NB
authors: Larson
authors: Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
authors: J
authors: J
authors: Davila
authors: Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
authors: C
authors: C
authors: Wang
authors: Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.
authors: M C
authors: MC
authors: Larson
authors: Department of Oncology, University of Cambridge, Cambridge, United Kingdom.
authors: H
authors: H
authors: Song
authors: Department of Oncology, University of Cambridge, Cambridge, United Kingdom.
authors: E M
authors: EM
authors: Dicks
authors: Department of Oncology, University of Cambridge, Cambridge, United Kingdom.
authors: P
authors: P
authors: Harrington
authors: Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota.
authors: M
authors: M
authors: Wick
authors: Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota.
authors: B J
authors: BJ
authors: Winterhoff
authors: Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, University of California at Los Angeles and Jonsson Comprehensive Cancer Center, Los Angeles, California.
authors: H
authors: H
authors: Hamidi
authors: Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine, University of California at Los Angeles and Jonsson Comprehensive Cancer Center, Los Angeles, California.
authors: G E
authors: GE
authors: Konecny
authors: Department of Translational Genomics, University of Kansas Medical Center, Kansas City, Kansas.
authors: J
authors: J
authors: Chien
authors: Illumina Corporation, San Diego, California.
authors: M
authors: M
authors: Bibikova
authors: Illumina Corporation, San Diego, California.
authors: J-B
authors: JB
authors: Fan
authors: Department of Medical Oncology, Mayo Clinic, Rochester, Minnesota.
authors: K R
authors: KR
authors: Kalli
authors: Department of Health Science Research, Medical Genetics, Mayo Clinic, Scottsdale, Arizona.
authors: N M
authors: NM
authors: Lindor
authors: Department of Biostatistics, University of Kansas Medical Center, Kansas City, Kansas.
authors: B L
authors: BL
authors: Fridley
authors: 1] Department of Oncology, University of Cambridge, Cambridge, United Kingdom [2] Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
authors: P P D
authors: PP
authors: Pharoah
authors: Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota.
authors: E L
authors: EL
authors: Goode
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001483:Base Sequence; D000077216:Carcinoma, Ovarian Epithelial; D019175:DNA Methylation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D059765:Homologous Recombination / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009375:Neoplasms, Glandular and Epithelial / Q000145:classification / Q000235:genetics* / Q000401:mortality; D010051:Ovarian Neoplasms / Q000145:classification / Q000235:genetics* / Q000401:mortality; D017422:Sequence Analysis, DNA
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D004268:DNA-Binding Proteins; C448305:RAD51C protein, human