engleski

NGS-based BRCA1, 2 mutation testing of high-grade serous ovarian carcinoma

Technological advances in the development of sequencing techniques have led to the increasing application of next- generation sequencing (NGS) in understanding the nature of many diseases and their improved treatment, especially for malignant diseases. An increasing amount of data shows that high-grade (HG) serous ovarian cancer patients carrying BRCA1 and BRCA2 mutations – both somatic and germline – experience a survival advantage and are more sensitive to agents such as platinum and PARP inhibitors. In the period 2016-2018 we analysed mutations of BRCA1, 2 genes in patients with HG- serous ovarian cancer, treated at the University Hospital Centre Split (n=80). Genomic DNA was isolated from blood, a library was prepared using the TruSeq Custom Amplicon Low Input Library Prep Kit and analysed on a MiniSeq Instrument (both Illumina, San Diego, CA, USA). Deleterious germline mutations were identified in 21 patients (26 %), 13 in the BRCA1 and 8 in the BRCA2 gene. The most common mutations in the BRCA1 gene were c.5266dupC (p.Gln1756ProfsV74) and c.843_846delCTCA (p.Ser282Tyrfs), found in 9 (42.85 %) and 2 patients, respectively. The most common mutation in the BRCA2 gene was c.9371A>T (p.Asn3124Ile), found in 2 patients (9.5 %). Numerous advantages of the NGS approach have been demonstrated, since it has proven to be highly sensitive, as have specific methods for BRCA mutation analysis in patients with HG-serous ovarian cancer, since it allows the simultaneous screening of multiple genes, reduces turnaround time of analysis, and requires a very low input of DNA

genomics ; malignant diseases ; next generation sequencing ; sensitivity of method

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