Detection of BRCA1/2 pathogenic variants in patients with breast and/or ovarian cancer and their families. Analysis of 3,458 cases from Lower Silesia (Poland) according to the diagnostic algorithm of the National Cancer Control Programme.

Breast and ovarian cancers are among the most common malignancies in the female population, with approximately 5-10% of cases being hereditary. and with other homologous recombination genes are the most tested genes in hereditary breast and ovarian cancer (HBOC) patients. As next-generation sequencing (NGS) has become a standard and popular technique, such as for HBOC, it has greatly simplified and accelerated molecular diagnosis of cancer. The study group included 3,458 HBOC patients or their relatives from Lower Silesia (Poland) (a voivodeship located in south-west Poland inhabited by 2.9 million people). All patients were tested according to the recommendations from the National Cancer Control Programme of the Ministry of Health for the years 2018-21. We tested 3,400 patients for recurrent pathogenic variants for the Polish population: five founder variants (c.5266dup, c.181T>G, c.4035del, c.3700_3704del, and c.68_69del), two variants (c.509_510del, c.172_175del) and three variants [c.1100del, c.444+1G>A, g.27417113-27422508del (del5395)]. Next 260 patients from the study group were chosen for the NGS panel, and additionally selected marker pathogenic variants were tested using Sanger sequencing and MLPA methods in 45 and 13 individuals, respectively. The analysis of in the 3,458 patients with HBOC or their relatives revealed 144 carriers of 37 different pathogenic variants (22 in and 15 in ). Among all detected variants, 71.53% constituted founder pathogenic variants. Our study has revealed that for the Lower Silesian population, the first-line molecular test may be limited to only three variants in -c.5266dup, c.181T>G, and c.4035del-but the aim should be to provide a full screening test of HBOC critical genes. The key and still growing role of molecular diagnostics of neoplasms, which includes HBOC, is undeniable. Therefore, it is necessary to provide complete and optimal therapeutic and prophylactic algorithms in line with current medical knowledge.