Advertisement

Discovery of BRCA1/BRCA2 founder variants by haplotype analysis

  • Author Footnotes
    1 These authors contributed equally to this work.
    Won Kyung Kwon
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 1 Irwon-ro, Gangnam-gu, Seoul 06351, South Korea
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.
    Hyeok-Jae Jang
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea
    Search for articles by this author
  • Jeong Eon Lee
    Affiliations
    Department of Surgery, Division of Breast Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
    Search for articles by this author
  • Yeon Hee Park
    Affiliations
    Department of Medicine, Division of Hematology/Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
    Search for articles by this author
  • Jai Min Ryu
    Affiliations
    Department of Surgery, Division of Breast Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
    Search for articles by this author
  • Jonghan Yu
    Affiliations
    Department of Surgery, Division of Breast Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
    Search for articles by this author
  • Ja-Hyun Jang
    Affiliations
    Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 1 Irwon-ro, Gangnam-gu, Seoul 06351, South Korea
    Search for articles by this author
  • Jong-Won Kim
    Correspondence
    Corresponding author at: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 1 Irwon-ro, Gangnam-gu, Seoul 06351, South Korea.
    Affiliations
    Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 1 Irwon-ro, Gangnam-gu, Seoul 06351, South Korea

    Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.

      Abstract

      A significant number of hereditary breast or ovarian cancers are caused by germline variants, mostly BRCA1/BRCA2 genes. Because genetic predispositions vary by ethnicity, several studies have reported founder variants of BRCA1/BRCA2 genes. Such founder variants were reported primarily based on their relevant population frequencies. We reviewed the variant data relating to BRCA1 and BRCA2 genes from January 2012 to March 2019 at Samsung Medical Center, Seoul, Korea. Among the cases with pathogenic variants (PVs) or likely pathogenic variants (LPVs), we defined recurrent variants as those found in more than five unrelated patients. Using single nucleotide polymorphisms, we analyzed patient haplotypes. There were 14 recurrent variants in the BRCA1 gene and seven variants in the BRCA2 gene. Of note, three variants in each gene were primarily detected in Korean populations. Among them, the c.5339T>C (p.Leu1780Pro) BRCA1 variant had a long block sized 74.5 kb. In BRCA2, the c.1399A>T (p.Lys467*) variant had a long block sized 35.5 kb. We suggest that BRCA1 c.5339T>C (p.Leu1780Pro) and BRCA2 c.1399A>T (p.Lys467*) are founder variants of the Korean population. These two recurrent variants were ethnicity-prevalent, primarily found in Korean populations, and the sizes of the linkage disequilibrium blocks are longer than others.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Cancer Genetics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Jung K.W.
        • Won Y.J.
        • Kong H.J.
        • Oh C.M.
        • Lee D.H.
        • Lee J.S.
        Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2011.
        Cancer Res Treat. 2014; 46: 109-123
        • Hong S.
        • Won Y.J.
        • Park Y.R.
        • Jung K.W.
        • Kong H.J.
        • Lee E.S.
        Cancer Statistics in Korea: incidence, mortality, survival, and prevalence in 2017.
        Cancer Res Treat. 2020; 52: 335-350
        • Ferlay J.
        • Soerjomataram I.
        • Dikshit R.
        • Eser S.
        • Mathers C.
        • Rebelo M.
        • Parkin D.M.
        • Forman D.
        • Bray F.
        Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012.
        Int J Cancer. 2015; 136: E359-E386
        • Miki Y.
        • Swensen J.
        • Shattuck-Eidens D.
        • Futreal P.A.
        • Harshman K.
        • Tavtigian S.
        • Liu Q.
        • Cochran C.
        • Bennett L.M.
        • Ding W.
        • et al.
        A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1.
        Science. 1994; 266: 66-71
        • Wooster R.
        • Bignell G.
        • Lancaster J.
        • Swift S.
        • Seal S.
        • Mangion J.
        • Collins N.
        • Gregory S.
        • Gumbs C.
        • Micklem G.
        Identification of the breast cancer susceptibility gene BRCA2.
        Nature. 1995; 378: 789-792
        • Kuchenbaecker K.B.
        • Hopper J.L.
        • Barnes D.R.
        • Phillips K.A.
        • Mooij T.M.
        • Roos-Blom M.J.
        • Jervis S.
        • van Leeuwen F.E.
        • Milne R.L.
        • Andrieu N.
        • Goldgar D.E.
        • Terry M.B.
        • Rookus M.A.
        • Easton D.F.
        • Antoniou A.C.
        • McGuffog L.
        • Evans D.G.
        • Barrowdale D.
        • Frost D.
        • Adlard J.
        • Ong K.R.
        • Izatt L.
        • Tischkowitz M.
        • Eeles R.
        • Davidson R.
        • Hodgson S.
        • Ellis S.
        • Nogues C.
        • Lasset C.
        • Stoppa-Lyonnet D.
        • Fricker J.P.
        • Faivre L.
        • Berthet P.
        • Hooning M.J.
        • van der Kolk L.E.
        • Kets C.M.
        • Adank M.A.
        • John E.M.
        • Chung W.K.
        • Andrulis I.L.
        • Southey M.
        • Daly M.B.
        • Buys S.S.
        • Osorio A.
        • Engel C.
        • Kast K.
        • Schmutzler R.K.
        • Caldes T.
        • Jakubowska A.
        • Simard J.
        • Friedlander M.L.
        • McLachlan S.A.
        • Machackova E.
        • Foretova L.
        • Tan Y.Y.
        • Singer C.F.
        • Olah E.
        • Gerdes A.M.
        • Arver B.
        • Olsson H.
        Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers.
        JAMA. 2017; 317: 2402-2416
        • Ford D.
        • Easton D.F.
        • Bishop D.T.
        • Narod S.A.
        • Goldgar D.E.
        Risks of cancer in BRCA1-mutation carriers. Breast cancer linkage consortium.
        Lancet. 1994; 343: 692-695
      1. Cancer risks in BRCA2 mutation carriers.
        J Natl Cancer Inst. 1999; 91: 1310-1316
        • Risch H.A.
        • McLaughlin J.R.
        • Cole D.E.
        • Rosen B.
        • Bradley L.
        • Fan I.
        • Tang J.
        • Li S.
        • Zhang S.
        • Shaw P.A.
        • Narod S.A.
        Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin-cohort study in Ontario, Canada.
        J Natl Cancer Inst. 2006; 98: 1694-1706
        • van der Kolk D.M.
        • de Bock G.H.
        • Leegte B.K.
        • Schaapveld M.
        • Mourits M.J.
        • de Vries J.
        • van der Hout A.H.
        • Oosterwijk J.C.
        Penetrance of breast cancer, ovarian cancer and contralateral breast cancer in BRCA1 and BRCA2 families: high cancer incidence at older age.
        Breast Cancer Res Treat. 2010; 124: 643-651
        • Iqbal J.
        • Ragone A.
        • Lubinski J.
        • Lynch H.T.
        • Moller P.
        • Ghadirian P.
        • Foulkes W.D.
        • Armel S.
        • Eisen A.
        • Neuhausen S.L.
        • Senter L.
        • Singer C.F.
        • Ainsworth P.
        • Kim-Sing C.
        • Tung N.
        • Friedman E.
        • Llacuachaqui M.
        • Ping S.
        • Narod S.A.
        The incidence of pancreatic cancer in BRCA1 and BRCA2 mutation carriers.
        Br J Cancer. 2012; 107: 2005-2009
        • Janavičius R.
        Founder BRCA1/2 mutations in the Europe: implications for hereditary breast-ovarian cancer prevention and control.
        EPMA J. 2010; 1: 397-412
        • Loizzi V.
        • Cicinelli E.
        • Santamaria F.
        • Murgia F.
        • Minicucci V.
        • Resta L.
        • Resta N.
        • Natalicchio M.I.
        • Ranieri G.
        • Cormio G.
        BRCAmut and "founder effect": a prospective study in a single academic institution.
        Oncotarget. 2018; 9: 22353-22358
        • Ossa C.A.
        • Torres D.
        Founder and recurrent mutations in BRCA1 and BRCA2 genes in latin American countries: state of the art and literature review.
        Oncologist. 2016; 21: 832-839
        • Kwong A.
        • Shin V.Y.
        • Ma E.S.
        • Chan C.T.
        • Ford J.M.
        • Kurian A.W.
        • Tai E.
        Screening for founder and recurrent BRCA mutations in Hong Kong and US Chinese populations.
        Hong Kong Med J. 2018; 24: 4-6
        • Tafe L.J.
        • Datto M.B.
        • Palomaki G.E.
        • Lacbawan F.L.
        Molecular testing for the BRCA1 and BRCA2 Ashkenazi Jewish founder mutations: a report on the College of American Pathologists proficiency testing surveys.
        Genet Med. 2015; 17: 58-62
        • Ferla R.
        • Calò V.
        • Cascio S.
        • Rinaldi G.
        • Badalamenti G.
        • Carreca I.
        • Surmacz E.
        • Colucci G.
        • Bazan V.
        • Russo A.
        Founder mutations in BRCA1 and BRCA2 genes.
        Ann Oncol. 2007; 18 (vi93-8)
        • Behl S.
        • Hamel N.
        • de Ladurantaye M.
        • Lepage S.
        • Lapointe R.
        • Mes-Masson A.M.
        • Foulkes W.D.
        Founder BRCA1/BRCA2/PALB2 pathogenic variants in French-Canadian breast cancer cases and controls.
        Sci Rep. 2020; 10: 6491
        • Bhaskaran S.P.
        • Huang T.
        • Rajendran B.K.
        • Guo M.
        • Luo J.
        • Qin Z.
        • Zhao B.
        • Chian J.
        • Li S.
        • Wang S.M.
        Ethnic-specific BRCA1/2 variation within Asia population: evidence from over 78 000 cancer and 40 000 non-cancer cases of Indian, Chinese, Korean and Japanese populations.
        J Med Genet. 2021; 58: 752-759
        • Labuda D.
        • Zietkiewicz E.
        • Labuda M.
        The genetic clock and the age of the founder effect in growing populations: a lesson from French Canadians and Ashkenazim.
        Am J Hum Genet. 1997; 61: 768-771
        • Fackenthal J.D.
        • Olopade O.I.
        Breast cancer risk associated with BRCA1 and BRCA2 in diverse populations.
        Nat Rev Cancer. 2007; 7: 937-948
        • Friedman L.S.
        • Szabo C.I.
        • Ostermeyer E.A.
        • Dowd P.
        • Butler L.
        • Park T.
        • Lee M.K.
        • Goode E.L.
        • Rowell S.E.
        • King M.C.
        Novel inherited mutations and variable expressivity of BRCA1 alleles, including the founder mutation 185delAG in Ashkenazi Jewish families.
        Am J Hum Genet. 1995; 57: 1284-1297
        • Richards S.
        • Aziz N.
        • Bale S.
        • Bick D.
        • Das S.
        • Gastier-Foster J.
        • Grody W.W.
        • Hegde M.
        • Lyon E.
        • Spector E.
        • Voelkerding K.
        • Rehm H.L.
        Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.
        Genet Med. 2015; 17: 405-424
        • Rebbeck T.R.
        • Friebel T.M.
        • Friedman E.
        • Hamann U.
        • et al.
        Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.
        Hum Mutat. 2018; 39: 593-620
        • Palmero E.I.
        • Carraro D.M.
        • Alemar B.
        • Moreira M.A.M.
        • et al.
        The germline mutational landscape of BRCA1 and BRCA2 in Brazil.
        Sci Rep. 2018; 8: 9188
        • Sekine M.
        • Nagata H.
        • Tsuji S.
        • Hirai Y.
        • Fujimoto S.
        • Hatae M.
        • Kobayashi I.
        • Fujii T.
        • Nagata I.
        • Ushijima K.
        • Obata K.
        • Suzuki M.
        • Yoshinaga M.
        • Umesaki N.
        • Satoh S.
        • Enomoto T.
        • Motoyama S.
        • Tanaka K.
        Mutational analysis of BRCA1 and BRCA2 and clinicopathologic analysis of ovarian cancer in 82 ovarian cancer families: two common founder mutations of BRCA1 in Japanese population.
        Clin Cancer Res. 2001; 7: 3144-3150
        • Heramb C.
        • Wangensteen T.
        • Grindedal E.M.
        • Ariansen S.L.
        • Lothe S.
        • Heimdal K.R.
        • Mæhle L.
        BRCA1 and BRCA2 mutation spectrum - an update on mutation distribution in a large cancer genetics clinic in Norway.
        Hered Cancer Clin Pract. 2018; 16: 3
        • Moon S.
        • Kim Y.J.
        • Han S.
        • Hwang M.Y.
        • Shin D.M.
        • Park M.Y.
        • Lu Y.
        • Yoon K.
        • Jang H.M.
        • Kim Y.K.
        • Park T.J.
        • Song D.S.
        • Park J.K.
        • Lee J.E.
        • Kim B.J.
        The Korea biobank array: design and identification of coding variants associated with blood biochemical traits.
        Sci Rep. 2019; 9: 1382
        • Hoffmann T.J.
        • Zhan Y.
        • Kvale M.N.
        • Hesselson S.E.
        • Gollub J.
        • Iribarren C.
        • Lu Y.
        • Mei G.
        • Purdy M.M.
        • Quesenberry C.
        • Rowell S.
        • Shapero M.H.
        • Smethurst D.
        • Somkin C.P.
        • Van den Eeden S.K.
        • Walter L.
        • Webster T.
        • Whitmer R.A.
        • Finn A.
        • Schaefer C.
        • Kwok P.Y.
        • Risch N.
        Design and coverage of high throughput genotyping arrays optimized for individuals of East Asian, African American, and Latino race/ethnicity using imputation and a novel hybrid SNP selection algorithm.
        Genomics. 2011; 98: 422-430
        • Stephens M.
        • Donnelly P.
        A comparison of bayesian methods for haplotype reconstruction from population genotype data.
        Am J Hum Genet. 2003; 73: 1162-1169
        • Stephens M.
        • Scheet P.
        Accounting for decay of linkage disequilibrium in haplotype inference and missing-data imputation.
        Am J Hum Genet. 2005; 76: 449-462
        • Stephens M.
        • Smith N.J.
        • Donnelly P.
        A new statistical method for haplotype reconstruction from population data.
        Am J Hum Genet. 2001; 68: 978-989
        • Marchini J.
        • Cutler D.
        • Patterson N.
        • Stephens M.
        • Eskin E.
        • Halperin E.
        • Lin S.
        • Qin Z.S.
        • Munro H.M.
        • Abecasis G.R.
        • Donnelly P.
        A comparison of phasing algorithms for trios and unrelated individuals.
        Am J Hum Genet. 2006; 78: 437-450
        • Hirasawa A.
        • Imoto I.
        • Naruto T.
        • Akahane T.
        • Yamagami W.
        • Nomura H.
        • Masuda K.
        • Susumu N.
        • Tsuda H.
        • Aoki D.
        Prevalence of pathogenic germline variants detected by multigene sequencing in unselected Japanese patients with ovarian cancer.
        Oncotarget. 2017; 8: 112258-112267
        • Son B.H.
        • Ahn S.H.
        • Kim S.W.
        • Kang E.
        • Park S.K.
        • Lee M.H.
        • Noh W.C.
        • Kim L.S.
        • Jung Y.
        • Kim K.S.
        • Noh D.Y.
        • Moon B.I.
        • Suh Y.J.
        • Lee J.E.
        • Choi D.H.
        • Kim S.Y.
        • Jung S.H.
        • Yom C.K.
        • Lee H.
        • Yang J.H.
        Prevalence of BRCA1 and BRCA2 mutations in non-familial breast cancer patients with high risks in Korea: the Korean Hereditary Breast Cancer (KOHBRA) Study.
        Breast Cancer Res Treat. 2012; 133: 1143-1152
        • Kroiss R.
        • Winkler V.
        • Bikas D.
        • Fleischmann E.
        • Mainau C.
        • Frommlet F.
        • Muhr D.
        • Fuerhauser C.
        • Tea M.
        • Bittner B.
        • Kubista E.
        • Oefner P.J.
        • Bauer P.
        • Wagner T.M.
        Younger birth cohort correlates with higher breast and ovarian cancer risk in European BRCA1 mutation carriers.
        Hum Mutat. 2005; 26: 583-589
        • Vogel K.J.
        • Atchley D.P.
        • Erlichman J.
        • Broglio K.R.
        • Ready K.J.
        • Valero V.
        • Amos C.I.
        • Hortobagyi G.N.
        • Lu K.H.
        • Arun B.
        BRCA1 and BRCA2 genetic testing in Hispanic patients: mutation prevalence and evaluation of the BRCAPRO risk assessment model.
        J Clin Oncol. 2007; 25: 4635-4641
        • Han S.H.
        • Lee K.R.
        • Lee D.G.
        • Kim B.Y.
        • Lee K.E.
        • Chung W.S.
        Mutation analysis of BRCA1 and BRCA2 from 793 Korean patients with sporadic breast cancer.
        Clin Genet. 2006; 70: 496-501
        • Park J.S.
        • Nam E.J.
        • Park H.S.
        • Han J.W.
        • Lee J.Y.
        • Kim J.
        • Kim T.I.
        • Lee S.T.
        Identification of a novel BRCA1 pathogenic mutation in Korean patients following reclassification of BRCA1 and BRCA2 variants according to the ACMG standards and guidelines using relevant ethnic controls.
        Cancer Res Treat. 2017; 49: 1012-1021
        • Laitman Y.
        • Friebel T.M.
        • Yannoukakos D.
        • Fostira F.
        • Konstantopoulou I.
        • Figlioli G.
        • Bonanni B.
        • Manoukian S.
        • Zuradelli M.
        • Tondini C.
        • Pasini B.
        • Peterlongo P.
        • Plaseska-Karanfilska D.
        • Jakimovska M.
        • Majidzadeh K.
        • Zarinfam S.
        • Loizidou M.A.
        • Hadjisavvas A.
        • Michailidou K.
        • Kyriacou K.
        • Behar D.M.
        • Molho R.B.
        • Ganz P.
        • James P.
        • Parsons M.T.
        • Sallam A.
        • Olopade O.I.
        • Seth A.
        • Chenevix-Trench G.
        • Leslie G.
        • McGuffog L.
        • Marafie M.J.
        • Megarbane A.
        • Al-Mulla F.
        • Rebbeck T.R.
        • Friedman E.
        The spectrum of BRCA1 and BRCA2 pathogenic sequence variants in Middle Eastern, North African, and South European countries.
        Hum Mutat. 2019; 40: e1-e23
        • Sanz D.J.
        • Acedo A.
        • Infante M.
        • Durán M.
        • Pérez-Cabornero L.
        • Esteban-Cardeñosa E.
        • Lastra E.
        • Pagani F.
        • Miner C.
        • Velasco E.A.
        A high proportion of DNA variants of BRCA1 and BRCA2 is associated with aberrant splicing in breast/ovarian cancer patients.
        Clin Cancer Res. 2010; 16: 1957-1967
        • Kim H.
        • Cho D.Y.
        • Choi D.H.
        • Choi S.Y.
        • Shin I.
        • Park W.
        • Huh S.J.
        • Han S.H.
        • Lee M.H.
        • Ahn S.H.
        • Son B.H.
        • Kim S.W.
        • Haffty B.G.
        Characteristics and spectrum of BRCA1 and BRCA2 mutations in 3,922 Korean patients with breast and ovarian cancer.
        Breast Cancer Res Treat. 2012; 134: 1315-1326
        • Steffensen A.Y.
        • Dandanell M.
        • Jønson L.
        • Ejlertsen B.
        • Gerdes A.M.
        • Nielsen F.C.
        • Hansen T.
        Functional characterization of BRCA1 gene variants by mini-gene splicing assay.
        Eur J Hum Genet. 2014; 22: 1362-1368
        • Kim Y.C.
        • Zhao L.
        • Zhang H.
        • Huang Y.
        • Cui J.
        • Xiao F.
        • Downs B.
        • Wang S.M.
        Prevalence and spectrum of BRCA germline variants in mainland Chinese familial breast and ovarian cancer patients.
        Oncotarget. 2016; 7: 9600-9612
        • Kang E.
        • Seong M.W.
        • Park S.K.
        • Lee J.W.
        • Lee J.
        • Kim L.S.
        • Lee J.E.
        • Kim S.Y.
        • Jeong J.
        • Han S.A.
        • Kim S.W.
        The prevalence and spectrum of BRCA1 and BRCA2 mutations in Korean population: recent update of the Korean Hereditary Breast Cancer (KOHBRA) study.
        Breast Cancer Res Treat. 2015; 151: 157-168
        • Wu X.
        • Wu L.
        • Kong B.
        • Liu J.
        • Yin R.
        • Wen H.
        • Li N.
        • Bu H.
        • Feng Y.
        • Li Q.
        • Lu X.
        • Wei J.
        • Zhu X.
        • Mills J.
        • Ellison G.
        • Gutjahr T.
        • Liu Y.
        The first nationwide multicenter prevalence study of germline BRCA1 and BRCA2 mutations in chinese ovarian cancer patients.
        Int J Gynecol Cancer. 2017; 27: 1650-1657
        • Kim D.H.
        • Cho C.H.
        • Kwon S.Y.
        • Ryoo N.H.
        • Jeon D.S.
        • Lee W.
        • Ha J.S.
        BRCA1/2 mutations, including large genomic rearrangements, among unselected ovarian cancer patients in Korea.
        J Gynecol Oncol. 2018; 29: e90
        • Ryu J.M.
        • Kang G.
        • Nam S.J.
        • Kim S.W.
        • Yu J.
        • Lee S.K.
        • Bae S.Y.
        • Park S.
        • Paik H.J.
        • Kim J.W.
        • Park S.S.
        • Lee J.E.
        • Kim S.W.
        Suggestion of BRCA1 c.5339T>C (p.L1780P) variant confer from 'unknown significance' to 'Likely pathogenic' based on clinical evidence in Korea.
        Breast. 2017; 33: 109-116
        • Choi D.H.
        • Lee M.H.
        • Bale A.E.
        • Carter D.
        • Haffty B.G.
        Incidence of BRCA1 and BRCA2 mutations in young Korean breast cancer patients.
        J Clin Oncol. 2004; 22: 1638-1645
        • Park H.S.
        • Ryu J.M.
        • Park J.S.
        • Im S.A.
        • Jung S.Y.
        • Kim E.K.
        • Park W.C.
        • Min J.W.
        • Lee J.
        • You J.Y.
        • Lee J.E.
        • Kim S.W.
        Clinicopathological features of Patients with the BRCA1 c.5339T>C (p.Leu1780Pro) variant.
        Cancer Res Treat. 2020; 52: 680-688
        • Ahn S.H.
        • Son B.H.
        • Yoon K.S.
        • Noh D.Y.
        • Han W.
        • Kim S.W.
        • Lee E.S.
        • Park H.L.
        • Hong Y.J.
        • Choi J.J.
        • Moon S.Y.
        • Kim M.J.
        • Kim K.H.
        • Kwak B.S.
        • Cho D.Y.
        BRCA1 and BRCA2 germline mutations in Korean breast cancer patients at high risk of carrying mutations.
        Cancer Lett. 2007; 245: 90-95
        • Park K.S.
        • Lee W.
        • Seong M.W.
        • Kong S.Y.
        • Lee K.A.
        • Ha J.S.
        • Cho E.H.
        • Han S.H.
        • Park I.
        • Kim J.W.
        A population-based analysis of BRCA1/2 genes and associated breast and ovarian cancer risk in Korean patients: a multicenter cohort study.
        Cancers (Basel). 2021; 13
        • Meindl A.
        Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population.
        Int J Cancer. 2002; 97: 472-480
        • Chaffee K.G.
        • Oberg A.L.
        • McWilliams R.R.
        • Majithia N.
        • Allen B.A.
        • Kidd J.
        • Singh N.
        • Hartman A.R.
        • Wenstrup R.J.
        • Petersen G.M.
        Prevalence of germ-line mutations in cancer genes among pancreatic cancer patients with a positive family history.
        Genet Med. 2018; 20: 119-127
        • Song W.H.
        • Kim S.H.
        • Joung J.Y.
        • Park W.S.
        • Seo H.K.
        • Chung J.
        • Lee K.H.
        Prostate cancer in a patient with a family history of BRCA mutation: a case report and literature review.
        J Korean Med Sci. 2017; 32: 377-381
        • Hayano T.
        • Matsui H.
        • Nakaoka H.
        • Ohtake N.
        • Hosomichi K.
        • Suzuki K.
        • Inoue I.
        Germline variants of prostate cancer in japanese families.
        PLoS One. 2016; 11e0164233
        • Kwong A.
        • Shin V.Y.
        • Au C.H.
        • Law F.B.
        • Ho D.N.
        • Ip B.K.
        • Wong A.T.
        • Lau S.S.
        • To R.M.
        • Choy G.
        • Ford J.M.
        • Ma E.S.
        • Chan T.L.
        Detection of germline mutation in hereditary breast and/or ovarian cancers by next-generation sequencing on a four-gene panel.
        J Mol Diagn. 2016; 18: 580-594
        • Borg A.
        • Haile R.W.
        • Malone K.E.
        • Capanu M.
        • Diep A.
        • Törngren T.
        • Teraoka S.
        • Begg C.B.
        • Thomas D.C.
        • Concannon P.
        • Mellemkjaer L.
        • Bernstein L.
        • Tellhed L.
        • Xue S.
        • Olson E.R.
        • Liang X.
        • Dolle J.
        • Børresen-Dale A.L.
        • Bernstein J.L.
        Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study.
        Hum Mutat. 2010; 31: E1200-E1240
        • Kwong A.
        • Shin V.Y.
        • Ho J.C.
        • Kang E.
        • Nakamura S.
        • Teo S.H.
        • Lee A.S.
        • Sng J.H.
        • Ginsburg O.M.
        • Kurian A.W.
        • Weitzel J.N.
        • Siu M.T.
        • Law F.B.
        • Chan T.L.
        • Narod S.A.
        • Ford J.M.
        • Ma E.S.
        • Kim S.W.
        Comprehensive spectrum of BRCA1 and BRCA2 deleterious mutations in breast cancer in Asian countries.
        J Med Genet. 2016; 53: 15-23
        • Maistro S.
        • Teixeira N.
        • Encinas G.
        • Katayama M.L.
        • Niewiadonski V.D.
        • Cabral L.G.
        • Ribeiro R.M.
        • Gaburo Junior N.
        • de Gouvêa A.C.
        • Carraro D.M.
        • Sabino E.C.
        • Diz M.D.
        • Chammas R.
        • de Bock G.H.
        • Folgueira M.A
        Germline mutations in BRCA1 and BRCA2 in epithelial ovarian cancer patients in Brazil.
        BMC Cancer. 2016; 16: 934
        • Blay P.
        • Santamaría I.
        • Pitiot A.S.
        • Luque M.
        • Alvarado M.G.
        • Lastra A.
        • Fernández Y.
        • Paredes A.
        • Freije J.M.
        • Balbín M.
        Mutational analysis of BRCA1 and BRCA2 in hereditary breast and ovarian cancer families from Asturias (Northern Spain).
        BMC Cancer. 2013; 13: 243
        • Kang H.C.
        • Kim I.J.
        • Park J.H.
        • Kwon H.J.
        • Won Y.J.
        • Heo S.C.
        • Lee S.Y.
        • Kim K.H.
        • Shin Y.
        • Noh D.Y.
        • Yang D.H.
        • Choe K.J.
        • Lee B.H.
        • King S.B.
        • Park J.G.
        Germline mutations of BRCA1 and BRCA2 in Korean breast and/or ovarian cancer families.
        Hum Mutat. 2002; 20: 235
        • Eoh K.J.
        • Kim J.E.
        • Park H.S.
        • Lee S.T.
        • Park J.S.
        • Han J.W.
        • Lee J.Y.
        • Kim S.
        • Kim S.W.
        • Kim J.H.
        • Kim Y.T.
        • Nam E.J.
        Detection of germline mutations in patients with epithelial ovarian cancer using multi-gene panels: beyond BRCA1/2.
        Cancer Res Treat. 2018; 50: 917-925
        • Jang J.H.
        • Lee J.E.
        • Kwon M.J.
        • Ki C.S.
        • Kim J.W.
        • Nam S.J.
        • Yang J.H.
        Spectra of BRCA1 and BRCA2 mutations in Korean patients with breast cancer: the importance of whole-gene sequencing.
        J Hum Genet. 2012; 57: 212-215
        • Seong M.W.
        • Cho S.
        • Noh D.Y.
        • Han W.
        • Kim S.W.
        • Park C.M.
        • Park H.W.
        • Kim S.Y.
        • Kim J.Y.
        • Park S.S.
        Comprehensive mutational analysis of BRCA1/BRCA2 for Korean breast cancer patients: evidence of a founder mutation.
        Clin Genet. 2009; 76: 152-160
        • Rebbeck T.R.
        • Friebel T.M.
        • Mitra N.
        • Wan F.
        • Chen S.
        • et al.
        Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women.
        Breast Cancer Res. 2016; 18: 112
        • George J.
        • Alsop K.
        • Etemadmoghadam D.
        • Hondow H.
        • Mikeska T.
        • Dobrovic A.
        • deFazio A.
        • Smyth G.K.
        • Levine D.A.
        • Mitchell G.
        • Bowtell D.D.
        Nonequivalent gene expression and copy number alterations in high-grade serous ovarian cancers with BRCA1 and BRCA2 mutations.
        Clin Cancer Res. 2013; 19: 3474-3484
        • Kwong A.
        • Ng E.K.
        • Wong C.L.
        • Law F.B.
        • Au T.
        • Wong H.N.
        • Kurian A.W.
        • West D.W.
        • Ford J.M.
        • Ma E.S.
        Identification of BRCA1/2 founder mutations in Southern Chinese breast cancer patients using gene sequencing and high resolution DNA melting analysis.
        PLoS One. 2012; 7: e43994
        • Yoshida R.
        • Watanabe C.
        • Yokoyama S.
        • Inuzuka M.
        • Yotsumoto J.
        • Arai M.
        • Nakamura S.
        Analysis of clinical characteristics of breast cancer patients with the Japanese founder mutation BRCA1 L63X.
        Oncotarget. 2019; 10: 3276-3284
        • Cornes B.K.
        • Tang C.S.
        • Leon T.Y.
        • Hui K.J.
        • So M.T.
        • Miao X.
        • Cherny S.S.
        • Sham P.C.
        • Tam P.K.
        • Garcia-Barcelo M.M.
        Haplotype analysis reveals a possible founder effect of RET mutation R114H for Hirschsprung's disease in the Chinese population.
        PLoS One. 2010; 5: e10918
        • Shinagawa J.
        • Moteki H.
        • Nishio S.Y.
        • Noguchi Y.
        • Usami S.I.
        Haplotype Analysis of GJB2 Mutations: founder Effect or Mutational Hot Spot?.
        Genes (Basel). 2020; : 11
        • Laitman Y.
        • Feng B.J.
        • Zamir I.M.
        • Weitzel J.N.
        • Duncan P.
        • Port D.
        • Thirthagiri E.
        • Teo S.H.
        • Evans G.
        • Latif A.
        • Newman W.G.
        • Gershoni-Baruch R.
        • Zidan J.
        • Shimon-Paluch S.
        • Goldgar D.
        • Friedman E.
        Haplotype analysis of the 185delAG BRCA1 mutation in ethnically diverse populations.
        Eur J Hum Genet. 2013; 21: 212-216
        • Benussi L.
        • Rademakers R.
        • Rutherford N.J.
        • Wojtas A.
        • Glionna M.
        • Paterlini A.
        • Albertini V.
        • Bettecken T.
        • Binetti G.
        • Ghidoni R.
        Estimating the age of the most common Italian GRN mutation: walking back to Canossa times.
        J Alzheimers Dis. 2013; 33: 69-76
        • Rannala B.
        • Bertorelle G.
        Using linked markers to infer the age of a mutation.
        Hum Mutat. 2001; 18: 87-100
        • Alvarez C.
        • Tapia T.
        • Perez-Moreno E.
        • Gajardo-Meneses P.
        • Ruiz C.
        • Rios M.
        • Missarelli C.
        • Silva M.
        • Cruz A.
        • Matamala L.
        • Carvajal-Carmona L.
        • Camus M.
        • Carvallo P.
        BRCA1 and BRCA2 founder mutations account for 78% of germline carriers among hereditary breast cancer families in Chile.
        Oncotarget. 2017; 8: 74233-74243
        • Roa B.B.
        • Boyd A.A.
        • Volcik K.
        • Richards C.S.
        Ashkenazi Jewish population frequencies for common mutations in BRCA1 and BRCA2.
        Nat Genet. 1996; 14: 185-187
        • Struewing J.P.
        • Hartge P.
        • Wacholder S.
        • Baker S.M.
        • Berlin M.
        • McAdams M.
        • Timmerman M.M.
        • Brody L.C.
        • Tucker M.A.
        The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews.
        N Engl J Med. 1997; 336: 1401-1408
        • Whittemore A.S.
        • Gong G.
        • John E.M.
        • McGuire V.
        • Li F.P.
        • Ostrow K.L.
        • Dicioccio R.
        • Felberg A.
        • West D.W.
        Prevalence of BRCA1 mutation carriers among U.S. non-Hispanic Whites.
        Cancer Epidemiol Biomark Prev. 2004; 13: 2078-2083
        • Vietri M.T.
        • Molinari A.M.
        • Caliendo G.
        • De Paola M.L.
        • Giovanna D.
        • Gambardella A.L.
        • Petronella P.
        • Cioffi M
        Double heterozygosity in the BRCA1 and BRCA2 genes in Italian family.
        Clin Chem Lab Med. 2013; 51: 2319-2324
        • Bang Y.J.
        • Kwon W.K.
        • Nam S.J.
        • Kim S.W.
        • Chae B.J.
        • Lee S.K.
        • et al.
        Clinicopathological characterization of double heterozygosity for BRCA1 and BRCA2 variants in Korean breast cancer patients.
        Cancer Res Treat. 2021; https://doi.org/10.4143/crt.2021.791
        • Adem C.
        • Reynolds C.
        • Soderberg C.L.
        • Slezak J.M.
        • McDonnell S.K.
        • Sebo T.J.
        • Schaid D.J.
        • Myers J.L.
        • Sellers T.A.
        • Hartmann L.C.
        • Jenkins R.B.
        Pathologic characteristics of breast parenchyma in patients with hereditary breast carcinoma, including BRCA1 and BRCA2 mutation carriers.
        Cancer. 2003; 97: 1-11