Spectrum and Prevalence of Pathogenic Variants in Ovarian Cancer Susceptibility Genes in a Group of 333 Patients

• Published in: Cancers 2018-11, Vol.10 (11), p.442
• Main Authors: Koczkowska, Magdalena, Krawczynska, Natalia, Stukan, Maciej, Kuzniacka, Alina, Brozek, Izabela, Sniadecki, Marcin, Debniak, Jaroslaw, Wydra, Dariusz, Biernat, Wojciech, Kozlowski, Piotr, Limon, Janusz, Wasag, Bartosz, Ratajska, Magdalena
• Format: Article
• Language: English
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers10110442

Constitutional loss-of-function pathogenic variants in the tumor suppressor genes and are widely associated with an elevated risk of ovarian cancer (OC). As only ~15% of OC individuals carry the pathogenic variants, the identification of other potential OC-susceptibility genes is of great clinical importance. Here, we established the prevalence and spectrum of the germline pathogenic variants in the and 23 other cancer-related genes in a large Polish population of 333 unselected OC cases. Approximately 21% of cases (71/333) carried the pathogenic or likely pathogenic variants, with c.5266dup (p.Gln1756Profs*74) and c.3700_3704del (p.Val1234Glnfs*8) being the most prevalent. Additionally, ~6% of women (20/333) were carriers of the pathogenic or likely pathogenic variants in other cancer-related genes, with and reported as the most frequently mutated, accounting for 1.8% (6/333) and 1.2% (4/333) of cases, respectively. We also found ten pathogenic or likely pathogenic variants in other genes: 1/333 in , 1/333 in , 2/333 in , 1/333 in , 1/333 in , 2/333 in , 1/333 in and 1/333 in , accounting for 50% of all detected variants in moderate- and low-penetrant genes. Our findings confirmed the presence of the additional OC-associated genes in the Polish population that may improve the personalized risk assessment of these individuals.