Abstract
BackgroundMutations in the BRCA1, BRCA2 and PALB2 genes are well-established risk factors for the development of breast and/or ovarian cancer. The frequency and spectrum of mutations in these genes has not yet been examined in the population of Southern Poland.MethodsWe examined the entire coding sequences of the BRCA1 and BRCA2 genes and genotyped a recurrent mutation of the PALB2 gene (c.509_510delGA) in 121 women with familial and/or early-onset breast or ovarian cancer from Southern Poland.ResultsA BRCA1 mutation was identified in 11 of 121 patients (9.1 %) and a BRCA2 mutation was identified in 10 of 121 patients (8.3 %). Two founder mutations of BRCA1 accounted for 91 % of all BRCA1 mutation carriers (c.5266dupC was identified in six patients and c.181 T > G was identified in four patients). Three of the seven different BRCA2 mutations were detected in two patients each (c.9371A > T, c.9403delC and c.1310_1313delAAGA). Three mutations have not been previously reported in the Polish population (BRCA1 c.3531delT, BRCA2 c.1310_1313delAAGA and BRCA2 c.9027delT). The recurrent PALB2 mutation c.509_510delGA was identified in two patients (1.7 %).ConclusionsThe standard panel of BRCA1 founder mutations is sufficiently sensitive for the identification of BRCA1 mutation carriers in Southern Poland. The BRCA2 mutations c.9371A > T and c.9403delC as well as the PALB2 mutation c.509_510delGA should be included in the testing panel for this population.
Highlights
Mutations in the BRCA1, BRCA2 and PALB2 genes are well-established risk factors for the development of breast and/or ovarian cancer
The BRCA1/2 proteins participate in molecular repair pathways in response to DNA damage; BRCA1 is involved in the recognition of DNA damage and the regulation of cell cycle arrest and BRCA2 regulates the key homologous recombination enzyme Rad51 [7,8,9,10,11,12,13,14]
Patient group We studied 121 women diagnosed with breast or ovarian cancer from families fulfilling one of the following criteria: 1) three or more breast and/or ovarian cancer cases in first or second-degree relatives, 2) synchronous or metachronous breast and/or ovarian cancer in the same patient, 3) two breast cancer cases in first-degree relatives or 4) breast cancer diagnosed before age 40
Summary
Mutations in the BRCA1, BRCA2 and PALB2 genes are well-established risk factors for the development of breast and/or ovarian cancer. The frequency and spectrum of mutations in these genes has not yet been examined in the population of Southern Poland. Inherited mutations in the DNA repair genes BRCA1 and BRCA2, discovered and cloned almost 20 years ago, are associated with significantly increased risks of both breast and ovarian cancer [1,2,3,4,5,6]. In Poland, a relatively small number of founder mutations in genes of high or moderate penetrance account for the majority of breast and/or ovarian cancer families. Among them are six mutations of BRCA1 Some recurrent mutations of Wojcik et al Hereditary Cancer in Clinical Practice (2016) 14:5
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