Mutational profile of hereditary breast and ovarian cancer – Establishing genetic testing guidelines in a developing country

Abstract

Purpose: Because many countries lack the capacity to follow the international guidelines for genetic testing, we suggest the specific approach for establishing local genetic testing guidelines that could be applied in developing countries. We focus on hereditary breast (BC) and ovarian cancer (OC) in Serbia. Methods: From the cohort of 550 persons who were referred for genetic counseling at the Institute for Oncology and Radiology of Serbia, 392 were selected. Personal and family histories were collected and germline DNA was sequenced with NGS in a panel of 20 genes. Results: Pathogenic (PV) and likely-pathogenic variants (LPV) were detected in 8 genes with the frequency of 23.7%. The most frequent were in BRCA1(7.6%), BRCA2(4.8%), PALB2(4.1%) and CHEK2(3.8%). They were also detected in ATM(1.8%), NBN(0.8%), TP53(0.5%) and RAD51C(0.3%). Whereas high carrier probability (CP), bilateral BC, BC and OC in the same patient and family history (FH) of BC/OC, were the strongest predictors for BRCA1/2 PV/LPV, lower CP values and early age of BC onset without FH were associated with higher frequency of PALB2 and CHEK2 PV/LPV. Conclusions: Population specific studies to identify specific mutational patterns and predictors of PV/LPV should be conducted in order to make scientifically sound and cost-effective guidelines for genetic testing in developing countries.