Reference Detail

Ref Type

Journal Article

PMID

(21822267)

Authors

Loveday C, Turnbull C, Ramsay E, Hughes D, Ruark E, Frankum JR, Bowden G, Kalmyrzaev B, Warren-Perry M, Snape K, Adlard JW, Barwell J, Berg J, Brady AF, Brewer C, Brice G, Chapman C, Cook J, Davidson R, Donaldson A, Douglas F, Greenhalgh L, Henderson A, Izatt L, Kumar A, Lalloo F, Miedzybrodzka Z, Morrison PJ, Paterson J, Porteous M, Rogers MT, Shanley S, Walker L, null null, Eccles D, Evans DG, Renwick A, Seal S, Lord CJ, Ashworth A, Reis-Filho JS, Antoniou AC, Rahman N

Title

Germline mutations in RAD51D confer susceptibility to ovarian cancer.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Nature genetics	43	9	2011 Aug 07	879-882	Nat Genet

URL

Abstract Text

Recently, RAD51C mutations were identified in families with breast and ovarian cancer. This observation prompted us to investigate the role of RAD51D in cancer susceptibility. We identified eight inactivating RAD51D mutations in unrelated individuals from 911 breast-ovarian cancer families compared with one inactivating mutation identified in 1,060 controls (P = 0.01). The association found here was principally with ovarian cancer, with three mutations identified in the 59 pedigrees with three or more individuals with ovarian cancer (P = 0.0005). The relative risk of ovarian cancer for RAD51D mutation carriers was estimated to be 6.30 (95% CI 2.86-13.85, P = 4.8 × 10(-6)). By contrast, we estimated the relative risk of breast cancer to be 1.32 (95% CI 0.59-2.96, P = 0.50). These data indicate that RAD51D mutation testing may have clinical utility in individuals with ovarian cancer and their families. Moreover, we show that cells deficient in RAD51D are sensitive to treatment with a PARP inhibitor, suggesting a possible therapeutic approach for cancers arising in RAD51D mutation carriers.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role
RAD51D	NCBI	BROVCA4\|R51H3\|RAD51L3\|TRAD		RAD51D, RAD51 paralog D, functions in homologous recombination in DNA repair and plays a role in telomere maintenance (PMID: 21821141, PMID: 23108668). Mutations in RAD51D are associated with increased susceptibility to ovarian cancer (PMID: 23372765, PMID: 21822267).	Unknown

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance
RAD51D	C9S	missense	unknown	RAD51D C9S lies within the region of the Rad51d protein that preferentially binds ssDNA (UniProt.org). C9S has been identified in the scientific literature (PMID: 22986143, PMID: 21822267, PMID: 25340522), but has not been biochemically characterized and therefore, its effect on Rad51d protein function is unknown (PubMed, Jun 2024).

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
RAD51D loss	Advanced Solid Tumor	sensitive	Olaparib	Preclinical	Actionable	In a preclinical study, cells harboring biallelic loss-of-function mutations in RAD51D had increased sensitivity to Lynparza (olaparib) compared to cells with wild-type RAD51D (PMID: 21822267).	21822267