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Am J Hum Genet. May 1997; 60(5): 1068–1078.
PMCID: PMC1712420

Moderate frequency of BRCA1 and BRCA2 germ-line mutations in Scandinavian familial breast cancer.


Previous studies of high-risk breast cancer families have proposed that two major breast cancer-susceptibility genes, BRCA1 and BRCA2, may account for at least two-thirds of all hereditary breast cancer. We have screened index cases from 106 Scandinavian (mainly southern Swedish) breast cancer and breast-ovarian cancer families for germ-line mutations in all coding exons of the BRCA1 and BRCA2 genes, using the protein-truncation test, SSCP analysis, or direct sequencing. A total of 24 families exhibited 11 different BRCA1 mutations, whereas 11 different BRCA2 mutations were detected in 12 families, of which 3 contained cases of male breast cancer. One BRCA2 mutation, 4486delG, was found in two families of the present study and, in a separate study, also in breast tumors from three unrelated males with unknown family history, suggesting that at least one BRCA2 founder mutation exists in the Scandinavian population. We report 1 novel BRCA1 mutation, eight additional cases of 4 BRCA1 mutations described elsewhere, and 11 novel BRCA2 mutations (9 frameshift deletions and 2 nonsense mutations), of which all are predicted to cause premature truncation of the translated products. The relatively low frequency of BRCA1 and BRCA2 mutations in the present study could be explained by insufficient screening sensitivity to the location of mutations in uncharacterized regulatory regions, the analysis of phenocopies, or, most likely, within predisposed families, additional uncharacterized BRCA genes.

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  • Chapman MS, Verma IM. Transcriptional activation by BRCA1. Nature. 1996 Aug 22;382(6593):678–679. [PubMed]
  • Cleton-Jansen AM, Collins N, Lakhani SR, Weissenbach J, Devilee P, Cornelisse CJ, Stratton MR. Loss of heterozygosity in sporadic breast tumours at the BRCA2 locus on chromosome 13q12-q13. Br J Cancer. 1995 Nov;72(5):1241–1244. [PMC free article] [PubMed]
  • Couch FJ, Farid LM, DeShano ML, Tavtigian SV, Calzone K, Campeau L, Peng Y, Bogden B, Chen Q, Neuhausen S, et al. BRCA2 germline mutations in male breast cancer cases and breast cancer families. Nat Genet. 1996 May;13(1):123–125. [PubMed]
  • Friedman LS, Ostermeyer EA, Szabo CI, Dowd P, Lynch ED, Rowell SE, King MC. Confirmation of BRCA1 by analysis of germline mutations linked to breast and ovarian cancer in ten families. Nat Genet. 1994 Dec;8(4):399–404. [PubMed]
  • Gayther SA, Warren W, Mazoyer S, Russell PA, Harrington PA, Chiano M, Seal S, Hamoudi R, van Rensburg EJ, Dunning AM, et al. Germline mutations of the BRCA1 gene in breast and ovarian cancer families provide evidence for a genotype-phenotype correlation. Nat Genet. 1995 Dec;11(4):428–433. [PubMed]
  • Gudmundsson J, Johannesdottir G, Arason A, Bergthorsson JT, Ingvarsson S, Egilsson V, Barkardottir RB. Frequent occurrence of BRCA2 linkage in Icelandic breast cancer families and segregation of a common BRCA2 haplotype. Am J Hum Genet. 1996 Apr;58(4):749–756. [PMC free article] [PubMed]
  • Jensen RA, Thompson ME, Jetton TL, Szabo CI, van der Meer R, Helou B, Tronick SR, Page DL, King MC, Holt JT. BRCA1 is secreted and exhibits properties of a granin. Nat Genet. 1996 Mar;12(3):303–308. [PubMed]
  • Johannsson O, Ostermeyer EA, Håkansson S, Friedman LS, Johansson U, Sellberg G, Brøndum-Nielsen K, Sele V, Olsson H, King MC, et al. Founding BRCA1 mutations in hereditary breast and ovarian cancer in southern Sweden. Am J Hum Genet. 1996 Mar;58(3):441–450. [PMC free article] [PubMed]
  • Kainu T, Kononen J, Johansson O, Olsson H, Borg A, Isola J. Detection of germline BRCA1 mutations in breast cancer patients by quantitative messenger RNA in situ hybridization. Cancer Res. 1996 Jul 1;56(13):2912–2915. [PubMed]
  • Lancaster JM, Wooster R, Mangion J, Phelan CM, Cochran C, Gumbs C, Seal S, Barfoot R, Collins N, Bignell G, et al. BRCA2 mutations in primary breast and ovarian cancers. Nat Genet. 1996 Jun;13(2):238–240. [PubMed]
  • Hieter P, Bassett DE, Jr, Valle D. The yeast genome--a common currency. Nat Genet. 1996 Jul;13(3):253–255. [PubMed]
  • Miki Y, Katagiri T, Kasumi F, Yoshimoto T, Nakamura Y. Mutation analysis in the BRCA2 gene in primary breast cancers. Nat Genet. 1996 Jun;13(2):245–247. [PubMed]
  • Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W, et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 1994 Oct 7;266(5182):66–71. [PubMed]
  • Neuhausen S, Gilewski T, Norton L, Tran T, McGuire P, Swensen J, Hampel H, Borgen P, Brown K, Skolnick M, et al. Recurrent BRCA2 6174delT mutations in Ashkenazi Jewish women affected by breast cancer. Nat Genet. 1996 May;13(1):126–128. [PubMed]
  • Olsson H, Alm P, Kristoffersson U, Landin-Olsson M. Hypophyseal tumor and gynecomastia preceding bilateral breast cancer development in a man. Cancer. 1984 May 1;53(9):1974–1977. [PubMed]
  • Phelan CM, Lancaster JM, Tonin P, Gumbs C, Cochran C, Carter R, Ghadirian P, Perret C, Moslehi R, Dion F, et al. Mutation analysis of the BRCA2 gene in 49 site-specific breast cancer families. Nat Genet. 1996 May;13(1):120–122. [PubMed]
  • Rebbeck TR, Couch FJ, Kant J, Calzone K, DeShano M, Peng Y, Chen K, Garber JE, Weber BL. Genetic heterogeneity in hereditary breast cancer: role of BRCA1 and BRCA2. Am J Hum Genet. 1996 Sep;59(3):547–553. [PMC free article] [PubMed]
  • Schutte M, da Costa LT, Hahn SA, Moskaluk C, Hoque AT, Rozenblum E, Weinstein CL, Bittner M, Meltzer PS, Trent JM, et al. Identification by representational difference analysis of a homozygous deletion in pancreatic carcinoma that lies within the BRCA2 region. Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):5950–5954. [PMC free article] [PubMed]
  • Shattuck-Eidens D, McClure M, Simard J, Labrie F, Narod S, Couch F, Hoskins K, Weber B, Castilla L, Erdos M, et al. A collaborative survey of 80 mutations in the BRCA1 breast and ovarian cancer susceptibility gene. Implications for presymptomatic testing and screening. JAMA. 1995 Feb 15;273(7):535–541. [PubMed]
  • Szabo CI, King MC. Inherited breast and ovarian cancer. Hum Mol Genet. 1995;4(Spec No):1811–1817. [PubMed]
  • Takahashi H, Chiu HC, Bandera CA, Behbakht K, Liu PC, Couch FJ, Weber BL, LiVolsi VA, Furusato M, Rebane BA, et al. Mutations of the BRCA2 gene in ovarian carcinomas. Cancer Res. 1996 Jun 15;56(12):2738–2741. [PubMed]
  • Tavtigian SV, Simard J, Rommens J, Couch F, Shattuck-Eidens D, Neuhausen S, Merajver S, Thorlacius S, Offit K, Stoppa-Lyonnet D, et al. The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds. Nat Genet. 1996 Mar;12(3):333–337. [PubMed]
  • Teng DH, Bogden R, Mitchell J, Baumgard M, Bell R, Berry S, Davis T, Ha PC, Kehrer R, Jammulapati S, et al. Low incidence of BRCA2 mutations in breast carcinoma and other cancers. Nat Genet. 1996 Jun;13(2):241–244. [PubMed]
  • Thorlacius S, Olafsdottir G, Tryggvadottir L, Neuhausen S, Jonasson JG, Tavtigian SV, Tulinius H, Ogmundsdottir HM, Eyfjörd JE. A single BRCA2 mutation in male and female breast cancer families from Iceland with varied cancer phenotypes. Nat Genet. 1996 May;13(1):117–119. [PubMed]
  • van den Berg J, Johannsson O, Håkansson S, Olsson H, Borg A. Allelic loss at chromosome 13q12-q13 is associated with poor prognosis in familial and sporadic breast cancer. Br J Cancer. 1996 Nov;74(10):1615–1619. [PMC free article] [PubMed]
  • 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 Dec 21;378(6559):789–792. [PubMed]
  • Wooster R, Neuhausen SL, Mangion J, Quirk Y, Ford D, Collins N, Nguyen K, Seal S, Tran T, Averill D, et al. Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science. 1994 Sep 30;265(5181):2088–2090. [PubMed]

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