Hereditary breast and ovarian cancer genetics: Genetic testing in Serbia

Breast cancer makes up 25% of all new cancers in women globally. Even though it usually occurs by chance (sporadic breast cancer), 5-10% of all breast cancer cases belong to hereditary breast cancer. It is usually characterized by many cancer cases (breast and/or ovarian), earlier age of onset, multiple primary and bilateral or multifocal cancers. Up to 30% of hereditary breast and ovarian cancers harbor a mutation in high risk breast cancer susceptibility genes BRCA1 or BRCA2. Besides BRCA genes, there are also other genes with the smaller effect on the risk. Since May 2016, 161 patients have been tested for the presence of mutations in the 19-gene panel at the Institute for Oncology and Radiology of Serbia. The majority of the mutations were in BRCA1 (15/161), BRCA2 (7/161) and PALB2 (7/161). Pathogenic mutations were also detected in ATM (2/161), CHEK2 (4/161) and TP53 (1/161). Variants of unclassified significance (VUS) were detected in BRCA2 (6/161), ATM (5/161), PMS2 (6/161), NBN (5/161) and PALB2 (5/161). 25 family members were tested for particular family mutation using targeted Sanger sequencing. Additional 6 mutations were detected in BRCA1, 1 in BRCA2, 3 in PALB2, 1 in CHEK2 and 1 in ATM gene. New sequencing technology lowered the cost of genetic testing and enabled higher access to genetic testing and genetic counseling for middle and lower-income countries. Our results of multi-gene germline testing showed the importance of widening the spectrum of the genes that should be offered for detecting hereditary predisposition in Serbia.