Abstract
IntroductionAccording to the National Cancer Register in Bulgaria more than 800 women develop ovarian cancer annually. The most frequent histological type, representing about three quarters of these cases is high-grade serous ovarian carcinoma (HS-OC). About 25% of the HG-OC are supposed to be caused by mutations in the BRCA1 and BRCA2 genes.Material and methodsWe have screened 80 Bulgarian patients with high grade serous ovarian cancer (HS-OC), disease progression and platinum sensitivity for germline mutations in the BRCA1/2 genes. The mutation analysis was performed by Next Generation Sequencing (NGS) with Ion Torrent PGM System, Sanger Sequencing and MLPA (Multiplex Ligation Dependent Probe Amplification). All identified pathogenic variants with NGS were confirmed by direct sequencing.Results and discussionsIn total 26 (32.5%) pathogenic mutations were found of which 23 (28.75%) in BRCA1: three recurrent c.5263_5264insC (7/80), c.2019delA (3/80), c.5333–1G>A (2/80), the rest appearing just once c.139T>C, c.139T>G, c.181T>G, c.3496delG, c.4391delC, c.5212G>A, c.5497G>A, c.5533_5534insT, deletion of exons 3–7. In BRCA2 only 4 (5%) mutations were found: c.3545_3546delTT, c.8059_8063delGTTCT, c.8674A>T, c.9294C>G. The most prevalent mutation in the study group observed with frequency of 8.75% was c.5263_5264insC, followed by c.2019delA (3.75%) and c.5333–1G>T (2.50%) in BRCA1. The recurrent mutations account for 57.7% of all detected mutations.ConclusionTwenty six (32.5%) of the HS-OC patients in our study were carriers of germline pathogenic mutations. These results are relevant to the clinical practice and personalised treatment of patients with OC. The BRCA1 and BRCA2 mutations are related to survival and chemotherapy response. The mutation carriers, detected by NGS sequencing, could benefit from therapy with PARP inhibitor.AcknowledgementsDUNK01-2/2009/NSF, Ministry of Education and Science, Bulgaria, AstraZeneca LTD, Bulgaria
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