Haplotype and phenotype analysis of nine recurrent BRCA2 mutations in 111 families: results of an international study

S L Neuhausen, A K Godwin, R Gershoni-Baruch, E Schubert, J Garber, D Stoppa-Lyonnet, E Olah, B Csokay, O Serova, F Lalloo, A Osorio, M Stratton, K Offit, J Boyd, M A Caligo, R J Scott, Andrew Craig Schofield, E Teugels, M Schwab, L Cannon-AlbrightT Bishop, D Easton, J Benitez, M C King, B A Ponder, B Weber, P Devilee, A Borg, S A Narod, D Goldgar

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135 Citations (Scopus)


Several BRCA2 mutations are found to occur in geographically diverse breast and ovarian cancer families. To investigate both mutation origin and mutation-specific phenotypes due to BRCA2, we constructed a haplotype of 10 polymorphic short tandem-repeat (STR) markers flanking the BRCA2 locus, in a set of 111 breast or breast/ovarian cancer families selected for having one of nine recurrent BRCA2 mutations. Six of the individual mutations are estimated to have arisen 400-2,000 years ago. In particular, the 6174delT mutation, found in approximately 1% of individuals of Ashkenazi Jewish ancestry, was estimated to have arisen 29 generations ago (1-LOD support interval 22-38). This is substantially more recent than the estimated age of the BRCA1 185delAG mutation (46 generations), derived from our analogous study of BRCA1 mutations. In general, there was no evidence of multiple origins of identical BRCA2 mutations. Our study data were consistent with the previous report of a higher incidence of ovarian cancer in families with mutations in a 3.3-kb region of exon 11 (the ovarian cancer cluster region [OCCR]) (P=.10); but that higher incidence was not statistically significant. There was significant evidence that age at diagnosis of breast cancer varied by mutation (P
Original languageEnglish
Pages (from-to)1381-1388
Number of pages8
JournalAmerican Journal of Human Genetics
Issue number6
Publication statusPublished - 1 Jun 1998


  • Adult
  • BRCA2 Protein
  • Breast Neoplasms
  • Breast Neoplasms, Male
  • Evolution, Molecular
  • Female
  • Genetic Markers
  • Genotype
  • Haplotypes
  • Humans
  • Male
  • Mutation
  • Neoplasm Proteins
  • Ovarian Neoplasms
  • Phenotype
  • Polymorphism, Genetic
  • Repetitive Sequences, Nucleic Acid
  • Transcription Factors
  • BRCA2
  • Breast cancer
  • Ovarian cancer
  • Mutation origin
  • Cancer, breast
  • Cancer, Ovarian


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