title: Identification of large genomic rearrangement of BRCA1/2 in high risk patients in Korea.
abstract: While the majority of germline inactivating mutations in BRCA1/2 are small-scale mutations, large genomic rearrangements (LGRs) are also detected in a variable proportion of patients. However, routine genetic methods are incapable of detecting LGRs, and comprehensive genetic testing algorithm is necessary.
  
  
  
  We performed multiplex ligation-dependent probe amplification assay for small-scale mutation negative patients at high-risk for LGR, based on previously published LGR risk criteria. The inclusion criteria for the high-risk subgroup were personal history of 1) early-onset breast cancer (diagnosed at ≤36 years); 2) two breast primaries; 3) breast cancer diagnosed at any age, with ≥1 close blood relatives (includes first-, second-, or third-degree) with breast and/or epithelial ovarian cancer; 4) both breast and epithelial ovarian cancer diagnosed at any age; and 5) epithelial ovarian cancer with ≥1 close blood relatives with breast and/or epithelial ovarian cancer.
  
  
  
  Two LGRs were identified. One was a heterozygous deletion of exon 19 and the other was a heterozygous duplication of exon 4-6. The prevalence of LGRs was 7% among Sanger-negative, high-risk patients, and accounted for 13% of all BRCA1 mutations and 2% of all patients. Moreover, LGRs reported in Korean patients, including our 2 newly identified cases, were found exclusively in families with at least one high-risk feature.
  
  
  
  Our result suggests that selective LGR screening for Sanger-negative, high-risk patients is necessary for Korean patients.
authors.affiliation: Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.|Department of Laboratory Medicine, Keimyung University School of Medicine, Daegu, South Korea.
authors.forename: Do-Hoon
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea. chez@catholic.ac.kr.|Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. chez@catholic.ac.kr.
authors.forename: Hyojin
authors.initials: H
authors.lastname: Chae
authors.affiliation: Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.|Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Irene
authors.initials: I
authors.lastname: Jo
authors.affiliation: Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.|Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Jaeeun
authors.initials: J
authors.lastname: Yoo
authors.affiliation: Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Hyeyoung
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.|Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Woori
authors.initials: W
authors.lastname: Jang
authors.affiliation: Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.|Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Joonhong
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.
authors.forename: Gun Dong
authors.initials: GD
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, Keimyung University School of Medicine, Daegu, South Korea.
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Jeon
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Keun Ho
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Hur
authors.affiliation: Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Byung Joo
authors.initials: BJ
authors.lastname: Chae
authors.affiliation: Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Byung Joo
authors.initials: BJ
authors.lastname: Song
authors.affiliation: Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.|Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Myungshin
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.|Catholic Genetic Laboratory Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Yonggoo
authors.initials: Y
authors.lastname: Kim
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D000077216:Carcinoma, Ovarian Epithelial; D004247:DNA / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D005091:Exons; D005260:Female; D015321:Gene Rearrangement; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology; D010375:Pedigree; D056910:Republic of Korea; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; D004247:DNA
keywords: BRCA1; BRCA2; Breast cancer; Genetic testing; Korea; Ovarian cancer