Germline mutations in cancer susceptibility genes in high grade serous ovarian cancer in Serbia


Clinical criteria for genetic testing of genes other than BRCA1/2 in epithelial ovarian cancer (EOC) still do not exist. We assessed the frequency and predictors of deleterious mutations in 19 cancer predisposition genes in high-grade serous ovarian cancer (HGSOC) in Serbia. Next-generation sequencing was used to identify germline mutations in the whole coding regions of a gene panel. Patients’ characteristics and sequencing data were summarized with descriptive statistics and compared using chi-square test. Among 131 HGSOC patients, 23 had BRCA1 (17.6%) while 5 had BRCA2 (3.8%) mutation. In addition, 9 (6.9%) pathogenic mutations were detected in other genes including BRIP1 (n = 2;1.5%), CHEK2 (n = 2;1.5%), NBN (n = 3;2.3%) and RAD51C (n = 2;1.5%). Factors that predicted for BRCA1/2 mutations were: breast and ovarian cancers in the same patient (p = 0.031), young age of EOC (p = 0.029), menstrual status (p = 0.004) and family history of cancer (p < 0.0001). However, these factors did not predict for mutations in other cancer susceptibility genes. Applying established referral criteria for genetic testing in Serbia will help identify BRCA1/2 mutation carriers but will not help identify mutations in other cancer susceptibility genes. Until better predictors emerge we should be performing wider genetic testing of EOC in order to identify all mutation carriers.

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This study was supported by a grant from the Ministry of Education, Science and Technological development of the Republic of Serbia (Grant number 41026)

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Correspondence to Ana Krivokuca.

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Krivokuca, A., Boljevic, I., Jovandic, S. et al. Germline mutations in cancer susceptibility genes in high grade serous ovarian cancer in Serbia. J Hum Genet 64, 281–290 (2019) doi:10.1038/s10038-019-0562-z

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