Mutation analysis of RAD51D in non-BRCA1/2 ovarian and breast cancer families

被引：36

作者：

Osher, D. J. ^{[1
,2
,3
]}

De Leeneer, K. ^{[4
]}

Michils, G. ^{[5
]}

Hamel, N. ^{[1
,2
,3
]}

Tomiak, E. ^{[6
,7
]}

Poppe, B. ^{[4
]}

Leunen, K. ^{[8
]}

Legius, E. ^{[5
]}

Shuen, A. ^{[1
,2
,3
]}

Smith, E. ^{[6
]}

Arseneau, J. ^{[9
]}

Tonin, P. ^{[1
,2
,10
,11
]}

Matthijs, G. ^{[5
]}

Claes, K. ^{[4
]}

Tischkowitz, M. D. ^{[1
,2
,12
]}

Foulkes, W. D. ^{[1
,2
,3
,12
]}

机构：

[1] McGill Univ, Program Canc Genet, Dept Oncol, Gerald Bronfman Ctr Clin Res Oncol, Montreal, PQ H2W 1S6, Canada

[2] McGill Univ, Program Canc Genet, Dept Human Genet, Gerald Bronfman Ctr Clin Res Oncol, Montreal, PQ H2W 1S6, Canada

[3] McGill Univ, Ctr Hlth, Dept Med Genet, Montreal, PQ H2W 1S6, Canada

[4] Ghent Univ Hosp, Ctr Med Genet, Ghent, Belgium

[5] Univ Leuven, Ctr Human Genet, Louvain, Belgium

[6] Childrens Hosp Eastern Ontario, Dept Genet, Ottawa, ON K1H 8L1, Canada

[7] Univ Ottawa, Fac Med, Ottawa, ON, Canada

[8] Univ Leuven, Univ Hosp Leuven, Dept Obstet & Gynecol, Div Gynecol Oncol, Louvain, Belgium

[9] McGill Univ, Dept Pathol, Ctr Hlth, Montreal, PQ H2W 1S6, Canada

[10] McGill Univ, Dept Med, Montreal, PQ H2W 1S6, Canada

[11] McGill Univ, Ctr Hlth, Res Inst, Montreal, PQ H2W 1S6, Canada

[12] McGill Univ, Jewish Gen Hosp, Segal Canc Ctr, Lady Davis Inst, Montreal, PQ H2W 1S6, Canada

来源：

BRITISH JOURNAL OF CANCER | 2012年 / 106卷 / 08期

关键词：

double-strand DNA repair; hereditary; ovarian carcinoma; PARP inhibitors; RAD51D; RAD51C; GERMLINE MUTATIONS; SUSCEPTIBILITY GENE; RISK;

D O I：

10.1038/bjc.2012.87

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

BACKGROUND: Recent data show that mutations in RAD51D have an aetiological role in ovarian carcinoma, yet mutations do not appear to be associated with an increased risk for breast cancer. We studied ovarian and breast cancer families having at least one woman affected by ovarian carcinoma, to assess the importance of RAD51D mutations in such families. METHODS: The coding region of the RAD51D gene was analysed in 175 BRCA1/2-negative families with family histories of both ovarian and breast cancer ascertained from two Canadian and two Belgian institutions. RESULTS: We identified one previously reported deleterious mutation, p. Arg186* (c.556C4T), and two novel variants; missense substitution p.Cys119Arg and an intronic variant c.83-26A>G. p.Arg186* segregated with the disease in the family and two ovarian carcinomas available for analysis showed loss of the wild-type allele, but the novel variants are likely neutral. CONCLUSION: RAD51D should be included in genetic screening of ovarian cancer families that do not have BRCA1/BRCA2 mutations. We show that mutations are more likely to be found in families with two or more ovarian cancers, or in probands with first-degree relatives with ovarian cancer, and we feel testing should be preferentially offered to affected women from such families. British Journal of Cancer (2012) 106, 1460-1463. doi: 10.1038/bjc.2012.87 www.bjcancer.com Published online 13 March 2012 (C) 2012 Cancer Research UK

引用

页码：1460 / 1463

页数：4

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