Abstract
Objective
RAD51D, a gene in the Fanconi Anemia–BRCA homologous recombination pathway, has recently
been shown to harbor germline mutations responsible for ovarian carcinoma in multiply
affected families. We aimed to extend these results to ovarian carcinoma in the general
population.
Methods
We sequenced RAD51D in germline DNA from 360 individuals with primary ovarian, peritoneal or fallopian
tube carcinoma who were not selected for age of cancer onset or family history. We
also sequenced RAD51D in 459 probands from 226 high risk breast cancer families who
were wild type for 21 breast and ovarian cancer genes.
Results
Of 360 cases, three (0.8%) carried loss-of-function mutations in RAD51D. All three subjects had ovarian carcinoma; one was also diagnosed with a synchronous
endometrial carcinoma. Only one of the three subjects had a family history of breast
or ovarian cancer. Combined with previous data for this series, 23.9% of women with
unselected ovarian, fallopian tube, or peritoneal carcinoma carried a germline loss-of-function
mutation in any of 13 tumor suppressor genes. Among the 449 women and 10 men with
familial breast cancer, none carried a loss of function mutation in RAD51D.
Conclusions
These data support the previous observation that loss-of-function mutations in RAD51D predispose to ovarian carcinoma but not to breast carcinoma. We conclude that inherited
ovarian cancer is highly heterogeneous genetically, and that approximately one in
four ovarian carcinoma patients carry a germline mutation in a known tumor suppressor
gene that confers high risk.
Highlights
- RAD51D loss-of-function mutations are present in 1% of unselected women with ovarian cancer.
- Ovarian cancer risk assessment should include evaluation of RAD51D in a multigene panel.
- Women with ovarian cancer should be evaluated for hereditary risk without selection for family history.
Keywords
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References
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Article info
Publication history
Accepted:
September 9,
2012
Received:
June 21,
2012
Identification
Copyright
© 2012 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
ScienceDirect
Access this article on ScienceDirectLinked Article
- Corrigendum to: Loss of function germline mutations in RAD51D in women with ovarian carcinoma [Gynecol Oncol 127: 552–555, 2012]Gynecologic OncologyVol. 132Issue 1
