Details

Autor(en) / Beteiligte

• NEUHAUSEN, S. L
• MAZOYER, S
• SOLOMON, E
• WEBER, B
• COUCH, F
• STRUEWING, J
• TONIN, P
• DUROCHER, F
• NAROD, S
• SKOLNICK, M. H
• LENOIR, G
• SEROVA, O
• FRIEDMAN, L
• PONDER, B
• STOPPA-LYONNET, D
• EASTON, D
• KING, M.-C
• GOLDGAR, D. E
• STRATTON, M
• OFFIT, K
• CALIGO, A
• TOMLINSON, G
• CANNON-ALBRIGHT, L
• BISHOP, T
• KELSELL, D

Titel

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

Ist Teil von

• American journal of human genetics, 1996-02, Vol.58 (2), p.271-280

Ort / Verlag

Chicago, IL: University of Chicago Press

Erscheinungsjahr

1996

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.