Objectives The aim of the study was to investigate the rate of concordance of germline BRCA1/2 (gBRCA1/2) with somatic BRCA1/2 (sBRCA1/2) pathogenic mutations to increase screening uptake for prescription of the newly NICE approved PARP inhibitor tablets available for gBRCA and sBRCA mutation carriers.
Methods 70 patients diagnosed with ovarian cancer were screened: 50 with High Grade Serous Carcinoma (HGSC), 2 Low Grade Serous Carcinoma (LGSC), 4 Clear Cell Carcinoma (CCC), 2 Carcinosarcoma, 11 Endometrioid Adenocarcinoma (EdAd) and 1 mucinous carcinoma. Patients were tested for BCRA1/2 germline mutations upfront, followed by testing of tumour specimens for somatic mutations using NGS.
Results 9 cases had gBRCA1/2 pathogenic mutations: 5 HGSC had gBRCA1, 3 HGSC and 1 EdAd had gBRCA2. 7 cases had sBRCA1/2 mutations: 4 gBRCA1 and 3 gBRCA2 HGSC had sBRCA1 and sBRCA2 respectively. EdAd gBRCA had no somatic mutations; 1 HGSC patient with gBRCA had no sBRCA mutations. 1 HGSC wild-type gBRCA showed pathogenic sBRCA1 frameshift mutation. 2 EdAd and 1 CCC wild-type gBRCA showed sBRCA1/2 mutations of unknown clinical significance. LGSC, carcinosaromas and mucinous carcinoma were wild-type gBRCA with no somatic mutations detected.
Conclusions Detection of both germline and somatic BRCA1/2 mutations is required for effective PARP inhibitors treatment. Somatic tests should be offered to increase the number of patients suitable for targeted therapy. The consistency of gBRCA uptake (13%) was in keeping with published data, whereas the sBRCA uptake was 11.4%, which is less than the expected 15%. More research into cases with sBRCA1/2 mutations of unknown clinical significance is warranted.
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