MUTYH-associated polyposis (MAP) is a rare hereditary condition caused by the biallelic mutation in the MUTYH gene encoding MUTYH glycosylase. This enzyme is a key member of the base excision repair (BER) pathway responsible for the repair of DNA lesions formed by reactive oxygen species (ROS). We report two cases of MAP. In case 1, a 67-year-old woman who presented with a personal history of colorectal and endometrial cancer and a family history of cancer syndromes underwent multigene panel testing that revealed a germline homozygous (biallelic) pathogenic variant c.1187G > A (p.Gly396Asp) in the MUTYH gene. Subsequent sequencing analysis performed in the offspring of the proband identified all three asymptomatic offspring as carriers of this pathogenic variant. In case 2, a 40-year-old woman with a strong family history of colorectal cancer [the proband’s sister was a carrier of the pathogenic variant c.536A > G (p.Tyr179Cys) of the MUTYH gene] and renal cancer underwent sequencing analysis of the MUTYH gene. The pathogenic heterozygous (monoallelic) variant c.536A > G (p.Tyr179Cys) of the MUTYH gene was identified in the proband. We found another pathogenic variant of the MUTYH gene—heterozygous (monoallelic) mutation c.1187G > A (p.Gly396Asp) in the genome of the proband’s husband. Molecular analysis of their offspring revealed that they are compound heterozygotes for MUTYH pathogenic variants c.536A > G (p.Tyr179Cys)/c.1187G > A (p.Gly396Asp). This paper shows the importance of genetic testing of asymptomatic relatives of the proband to ensure an early surveillance and management of individuals positive for pathogenic variant (s) in the MUTYH gene.

The average risk of breast cancer in general Slovak population of women is 4-5% and the risk of ovarian cancer is 2%. Probability of breast/ovarian cancer development is higher in individuals carrying a causative germline DNA variant in BRCA1 or BRCA2 gene responsible for hereditary breast/ovarian cancer (HBOC). Although a major proportion of inherited breast/ovarian cancers are due to the mentioned causal mutations, a number of new genes have emerged. Here we describe a rapid, multiplex and comprehensive approach for the detection of pathogenic variants in BRCA1 and BRCA2 genes which most frequently occur in Slovak HBOC population. Analysis comprises the combination of mutation specific methods. Fluorescent PCR amplification followed by fragment analysis for detection of insertions/deletions in exon 11 of BRCA1 gene. Second method is SNaPshot analysis for detection of the most frequent missense and ins/del variants in exons 2, 5, 13, 20 of BRCA1 and exons 11, 23 and 25 of BRCA2 gene. Altogether, we have analyzed 687 samples, 86 (12.5%) in group 1, which fulfilled indication criteria based on the positive family/personal history. Group 2 involved 601 (87.5%) cases, who did not meet the indication criteria and only the screening test was recommended. Using the combined approach, we have identified 47 mutated samples (6.8%), 40 in group 1 (46.5%) and 7 in group 2 (1.1%). However, the presented screening test would not provide complex results of BRCA1/2 gene analysis, it offers testing accessible to a broader spectrum of individuals under the threshold of indication for whole gene analysis. This approach may provide valuable information even in the NGS analysis era.

5 Klinika onkologickej chirurgie LF UK a OUSA, Bratislava 6 Oddelenie imunodiagnostiky OUSA a Vysoká škola zdravotníctva a sociálnej práce sv. Alžbety, Bratislava Feochromocytóm je katecholamíny produkujúci neuroendokrinný nádor vychádzajúci z chromafinných buniek drene nadobličky. Záchyt týchto nádorov je mimoriadne dôležitý, pretože sú spojené s vysokou kardiovaskulárnou morbiditou a mortalitou. Vďaka pokrokom v molekulárnej genetike sa vie, že až 35 % feochromocytómov je podmienených geneticky. Lynchov syndróm (hereditárny nepolypózny karcinóm kolorekta -HNPCC) patrí medzi autozomálne dominantné dedičné ochorenia, pričom nositelia patogénnych variantov majú predispozíciu na vznik kolorektálneho karcinómu alebo ďalších extrakolonických nádorov (adenokarcinómy endometria, žalúdka, karcinómy vaječníkov, močového traktu, tenkého čreva, nádory mozgu a kože). V zahraničných periodikách pribúdajú kazuistiky súbežného výskytu pacientov s HNPCC a neuroendokrinnými nádormi včítane feochromocytómu, predostierajúce otázku, či by tento typ nádoru mohol predstavovať ďalší extrakolonický prejav Lynchovho syndrómu.

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