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. 1996 Feb;58(2):271–280.

Haplotype and phenotype analysis of six recurrent BRCA1 mutations in 61 families: results of an international study.

S L Neuhausen 1, S Mazoyer 1, L Friedman 1, M Stratton 1, K Offit 1, A Caligo 1, G Tomlinson 1, L Cannon-Albright 1, T Bishop 1, D Kelsell 1, E Solomon 1, B Weber 1, F Couch 1, J Struewing 1, P Tonin 1, F Durocher 1, S Narod 1, M H Skolnick 1, G Lenoir 1, O Serova 1, B Ponder 1, D Stoppa-Lyonnet 1, D Easton 1, M C King 1, D E Goldgar 1
PMCID: PMC1914544  PMID: 8571953

Abstract

Several BRCA1 mutations have now been found to occur in geographically diverse breast and ovarian cancer families. To investigate mutation origin and mutation-specific phenotypes due to BRCA1, we constructed a haplotype of nine polymorphic markers within or immediately flanking the BRCA1 locus in a set of 61 breast/ovarian cancer families selected for having one of six recurrent BRCA1 mutations. Tests of both mutations and family-specific differences in age at diagnosis were not significant. A comparison of the six mutations in the relative proportions of cases of breast and ovarian cancer was suggestive of an effect (P = .069), with 57% of women presumed affected because of the 1294 del 40 BRCA1 mutation having ovarian cancer, compared with 14% of affected women with the splice-site mutation in intron 5 of BRCA1. For the BRCA1 mutations studied here, the individual mutations are estimated to have arisen 9-170 generations ago. In general, a high degree of haplotype conservation across the region was observed, with haplotype differences most often due to mutations in the short-tandem-repeat markers, although some likely instances of recombination also were observed. For several of the instances, there was evidence for multiple, independent, BRCA1 mutational events.

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Selected References

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