Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene

  title={Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene},
  author={Alfons Meindl and Heide Hellebrand and Constanze Wiek and Verena Erven and Barbara Wappenschmidt and Dieter Niederacher and Marcel Freund and Peter Lichtner and Linda Hartmann and Heiner Schaal and Juliane Ramser and Ellen Honisch and Christian Kubisch and H Erich Wichmann and Karin Kast and Helmut Deissler and Christoph Engel and Bertram M{\"u}ller-Myhsok and Kornelia Neveling and Marion Kiechle and Christopher G. Mathew and Detlev Schindler and Rita Schmutzler and Helmut Hanenberg},
  journal={Nature Genetics},
Germline mutations in a number of genes involved in the recombinational repair of DNA double-strand breaks are associated with predisposition to breast and ovarian cancer. RAD51C is essential for homologous recombination repair, and a biallelic missense mutation can cause a Fanconi anemia–like phenotype. In index cases from 1,100 German families with gynecological malignancies, we identified six monoallelic pathogenic mutations in RAD51C that confer an increased risk for breast and ovarian… 

Germline RAD51C mutations in ovarian cancer susceptibility

The results confirm that RAD51C is a susceptibility gene for ovarian and BC and that this gene should be screened for mutations in families with multiple BC/OC.

Evaluation of RAD51C as cancer susceptibility gene in a large breast-ovarian cancer patient population referred for genetic testing

A low prevalence of RAD51C mutations with an exception for some founder populations is suggested and this observation is in favor of the rare allele hypothesis in the debate over the nature of the genetic contribution to individual susceptibility to breast and ovarian cancer.

RAD51C germline mutations found in Spanish site-specific breast cancer and breast-ovarian cancer families

It is suggested that RAD51C testing should be offered to hereditary breast and/or ovarian cancer families without selecting for specific cancer origin, and prophylactic bilateral salpingo-ophorectomy in premenopausal RAD 51C mutation carriers is recommended.

Screening RAD51C nucleotide alterations in patients with a family history of breast and ovarian cancer

It has been reported that one biallelic missense mutation in the RAD51C gene was found in a Fanconi anemia-like disorder and six monoallelic pathogenic mutations were identified in 480 BRCA1/2

RAD51C Germline Mutations in Breast and Ovarian Cancer Cases from High-Risk Families

BRCA1 and BRCA2 are the most well-known breast cancer susceptibility genes. Additional genes involved in DNA repair have been identified as predisposing to breast cancer. One such gene, RAD51C, is

Germline mutation in the RAD51B gene confers predisposition to breast cancer

This study identified the first RAD51B mutation in a breast and ovarian cancer family and is the first report of XRCC3 mutation analysis in breast and Ovarian cancer.

RAD51C germline mutations in Chinese women with familial breast cancer

This study screened the entire coding regions and exon–intron boundaries of the RAD51C gene in 273 Chinese women with familial breast cancer who do not carry mutations in BRCA1 and BRCa2 genes by polymerase chain reaction (PCR)-sequencing and detected eight germline sequence variants in the RAD 51C gene.

Germline mutations in RAD51C in Jewish high cancer risk families

Germline mutations in RAD51C contribute marginally to breast and ovarian cancer susceptibility in ethnically diverse, Jewish high risk families.

RAD51 and Breast Cancer Susceptibility: No Evidence for Rare Variant Association in the Breast Cancer Family Registry Study

The data suggest that RAD51 tolerates so little dysfunctional sequence variation that rare variants in the gene contribute little, if anything, to breast cancer susceptibility.

Mutation screening of RAD51C in high-risk breast and ovarian cancer families

It is suggested that RAD51C mutations are rare events among high-risk breast cancer and breast/ovarian cancer families and large population-based studies will be needed to reliably assess the prevalence and penetrance of inactivating mutations in the RAD 51C susceptibility gene.



Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population

  • A. Meindl
  • Biology
    International journal of cancer
  • 2002
The main focus of this German‐wide multi‐center study was to establish a BRCA1/2 mutation profile and to determine family types with high frequencies of mutations in these genes and to provide strong evidence for further predisposing genes in the German population.

Ten genes for inherited breast cancer.

MLPA screening in the BRCA1 gene from 1,506 German hereditary breast cancer cases: novel deletions, frequent involvement of exon 17, and occurrence in single early‐onset cases

Advice is given for restricting BRCA1 MLPA screening to those subgroups that revealed LGRs and recommend BRCa2MLPA screening only for families presenting with cooccurrence of female and male breast cancer.

Pathology of Ovarian Cancers in BRCA1 and BRCA2 Carriers

Tumors in BRCA1 mutation carriers were more likely than tumors in age-matched controls to be invasive serous adenocarcinomas and may be expected to have poor prognosis, although this may be treatment dependent.

Genetic predisposition to breast cancer: past, present, and future.

The known genetic predisposition factors are described, the methods by which they were identified are expound on, and how further technological and intellectual advances may assist in identifying the remaining genetic factors underlying breast cancer susceptibility are considered.

The RAD51 gene family, genetic instability and cancer.

Breast and Ovarian Cancer Risks Due to Inherited Mutations in BRCA1 and BRCA2

Physical exercise and lack of obesity in adolescence were associated with significantly delayed breast cancer onset, and risks appear to be increasing with time.

Mutation of the RAD51C gene in a Fanconi anemia–like disorder

Biallelic germline mutations in a RAD51 paralog are associated with an FA-like syndrome because of loss of RAD51 focus formation in response to DNA damage and in increased cellular sensitivity to the DNA interstrand cross-linking agent mitomycin C and the topoisomerase-1 inhibitor camptothecin.

Prediction of BRCA1 Status in Patients with Breast Cancer Using Estrogen Receptor and Basal Phenotype

The use of cytokeratin staining in combination with ER and morphology provides a more accurate predictor of BRCA1 mutation status than previously available, that may be useful in selecting patients for BRCa1 mutation testing.

Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations.

Key features of the histologic phenotypes of breast cancers in carriers of mutant BRCA1 and BRCa2 genes are identified and this information may improve the classification of breast cancer in individuals with a family history of the disease and may ultimately aid in the clinical management of patients.