270 Large single-site institution experience of testing for somatic and germline concordance BRCA1/2 pathogenic mutations in ovarian cancer patients eligible for PARP inhibitors therapy. (18th September 2019)

• Record Type: Journal Article
• Authors: Akaev, I; Chau, C; Dabab, N; Rahimi, S; Gardner, F; Yeoh, CC
• Is Part Of: International journal of gynecological cancer. Volume 29(2019)Supplement 3
• Page Start: A114
• Page End: A114
• Publication Date: 2019-09-18
• Subjects: Generative organs, Female -- Cancer -- Periodicals; 616.99465
• DOI: 10.1136/ijgc-2019-IGCS.270
• Languages: English
• ISSNs: 1048-891X

Abstract

Abstract : 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.