title: Germline Mutations of BRCA1 and BRCA2 in Korean Ovarian Cancer Patients: Finding Founder Mutations.
abstract: OBJECTIVE
  To investigate and analyze the BRCA mutations in Korean ovarian cancer patients with or without family history and to find founder mutations in this group.
  
  
  METHODS
  One hundred two patients who underwent a staging operation for pathologically proven epithelial cancer between January 2013 and December 2014 were enrolled. Thirty-two patients declined to analyze BRCA1/2 gene alterations after genetic counseling and pedigree analysis. Lymphocyte specimens from peripheral blood were assessed for BRCA1/2 by direct sequencing.
  
  
  RESULTS
  BRCA genetic test results of 70 patients were available. Eighteen BRCA1/2 mutations and 17 unclassified variations (UVs) were found. Five of the BRCA1/2 mutations and 4 of the UVs were not reported in the Breast Cancer Information Core database. One BRCA2 UV (8665_8667delGGA) was strongly suspicious to be a deleterious mutation. BRCA1/2 mutations were identified in 11 (61.1%) of 18 patients with a family history and in 7 (13.5%) of 52 patients without a family history.Candidates for founder mutations in Korean ovarian cancer patients were assessed among 39 BRCA1/2 mutations from the present study and from literature reviews. The analysis showed that 1041_1043delAGCinsT (n = 4; 10.2%) and 3746insA (n = 4; 10.2%) were possible BRCA1 founder mutations. Only one of the BRCA2 mutations (5804_5807delTTAA) was repeated twice (n = 2; 5.1%).
  
  
  CONCLUSIONS
  The prevalence of BRCA1/2 mutations in Korean ovarian cancer patients irrespective of the family history was significantly higher than previously reported. Possible founder mutations in Korean ovarian cancer patients were identified.
authors.affiliation: *Comprehensive Gynecologic Cancer Center, Departments of Obstetrics and Gynecology and †Pathology, CHA Bundang Medical Center, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea; and ‡GreenCross Laboratories, Yongin City, Republic of Korea.
authors.forename: Min Chul
authors.initials: MC
authors.lastname: Choi
authors.forename: Jin-Hyung
authors.initials: JH
authors.lastname: Heo
authors.forename: Ja-Hyun
authors.initials: JH
authors.lastname: Jang
authors.forename: Sang Geun
authors.initials: SG
authors.lastname: Jung
authors.forename: Hyun
authors.initials: H
authors.lastname: Park
authors.forename: Won Duk
authors.initials: WD
authors.lastname: Joo
authors.forename: Chan
authors.initials: C
authors.lastname: Lee
authors.forename: Je Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Jun Mo
authors.initials: JM
authors.lastname: Lee
authors.forename: Yoon Young
authors.initials: YY
authors.lastname: Hwang
authors.forename: Seung Jo
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000473:pathology; D004252:DNA Mutational Analysis; D016889:Endometrial Neoplasms / Q000235:genetics / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D018703:Founder Effect; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D056910:Republic of Korea
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human