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| Haplotype and phenotype analysis of six recurrent BRCA1 mutations in 61 families: Results of an international study |
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| Author(s): Neuhausen SL, Mazoyer S, Friedman L, Stratton M, Offit K, Caligo A, Tomlinson G, CannonAlbright L, Bishop T, Kelsell D, Solomon E, Weber B, Couch F, Struewing J, Tonin P, Durocher F, Narod S, Skolnick MH, Lenoir G, Serova O, Ponder B, StoppaLyonnet D, Easton D, King MC, Goldgar DE |
| Source: AMERICAN JOURNAL OF HUMAN GENETICS Volume: 58 Issue: 2 Pages: 271-280 Published: FEB 1996 |
| Times Cited: 173 References: 22 |
| 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. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV UTAH, SCH MED, DEPT MED INFORMAT, GENET EPIDEMIOL GRP, SALT LAKE CITY, UT 84108 USA
2. UNIV UTAH, SCH MED, DEPT INTERNAL MED, SALT LAKE CITY, UT USA
3. MYRIAD GENET, SALT LAKE CITY, UT USA
4. UNIV CAMBRIDGE, DEPT PATHOL, CRC, HUMAN CANC GENET RES GRP, CAMBRIDGE, ENGLAND
5. UNIV CALIF BERKELEY, DEPT MOLEC & CELL BIOL, BERKELEY, CA 94720 USA
6. UNIV CALIF BERKELEY, SCH PUBL HLTH, BERKELEY, CA 94720 USA
7. INST CANC RES, SECT MOLEC CARCINOGENESIS, SUTTON, SURREY ENGLAND
8. INST CANC RES, EPIDEMIOL SECT, SUTTON, SURREY ENGLAND
9. MEM SLOAN KETTERING CANC CTR, DEPT HUMAN GENET, NEW YORK, NY 10021 USA
10. INST ANAT PATOL, PISA, ITALY
11. SW TEXAS STATE UNIV, DEPT PEDIAT, DALLAS, TX USA
12. IMPERIAL CANC RES FUND, GENET EPIDEMIOL LAB, LEEDS, W YORKSHIRE ENGLAND
13. IMPERIAL CANC RES FUND, CLARE HALL LABS, LONDON, ENGLAND
14. IMPERIAL CANC RES FUND, LINCOLNS INN FIELDS, LONDON, ENGLAND
15. UNIV PENN, DEPT HEMATOL ONCOL, PHILADELPHIA, PA 19104 USA
16. NATL CANC INST, GENET EPIDEMIOL BRANCH, BETHESDA, MD USA
17. NIH, BETHESDA, MD USA
18. MCGILL UNIV, DEPT MED GENET, MONTREAL, PQ CANADA
19. CHU LAVAL, RES CTR, DEPT MOLEC ENDOCRINOL, QUEBEC CITY, PQ CANADA
20. UNIV LAVAL, QUEBEC CITY, PQ CANADA
21. INT AGCY RES CANC, F-69372 LYON, FRANCE
22. INST CURIE, UNITE GENET ONCOL, PARIS, FRANCE |
| Publisher: UNIV CHICAGO PRESS, 5720 S WOODLAWN AVE, CHICAGO, IL 60637 |
| Subject Category: Genetics & Heredity |
| IDS Number: TR791 |
| ISSN: 0002-9297 |
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