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首页> 外文期刊>Balkan journal of medical genetics: BJMG >Molecular basis of inherited colorectal carcinomas in the Macedonian population: An update
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Molecular basis of inherited colorectal carcinomas in the Macedonian population: An update

机译：Macedonian人群中遗传结肠直肠癌的分子基础：更新

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Hereditary factors are assumed to play a role in ~35.0-45.0% of all colorectal cancers (CRCs) with about 5.0-10.0% associated with high penetrant disease-causing mutations in genes correlated to hereditary polyposis (HP) or hereditary non polyposis syndromes (HNPCC). Although inherited germline mutations in mismatch repair (MMR) and the APC genes contribute significantly to CRC, genetic diagnosis cannot yet be obtained in more than 50.0% of familial cases. We present updated data of 107 probands from the Macedonian population with clinically diagnosed HP (n = 41) or HNPCC (n = 66) obtained by next generation sequencing (NGS) with three different gene panels covering the coding, flanking and promoter regions of 114 cancer predisposition genes. Using this approach, we were able to detect deleterious mutations in 65/107 (60.7%) patients, 50.4% of which were in known well-established CRC susceptibility genes and 10.2% in DNA repair genes (DRG). As expected, the highest frequencies of deleterious variants were detected in familial adenomatous polyposis (FAP) and in HNPCC patients with microsatellite instability (MSI) tumors (93.8 and 87.1%, respectively). Variants of unknown significance (VUS) were detected in 24/107 (22.4%) patients, mainly in HNPCC patients with microsatellite stable (MSS) tumors or patients with oligopolyposis. The majority of VUS were also found in DRG genes, indicating the potential role of a doble-strand brake DNA repair pathway deficiency in colorectal cancerogenesis. We could not detect any variant in 18/107 (16.8%) patients, which supports the genetic heterogeneity of hereditary CRC, particularly in HNPCC families with MSS tumors and in families with oligopolyposis.
机译：假设遗传因素在〜35.0-45.0％的所有结肠直肠癌（CRC）中发挥作用，大约5.0-10.0％与与遗传息肉（HP）或遗传性非息肉综合征（ HNPCC）。虽然在不匹配修复（MMR）和APC基因中遗传的种系突变对CRC有贡献显着贡献，但遗传诊断尚不能获得50.0％的家族病例。我们将Macedonian群体的107个证据的最新数据与下一代测序（NGS）获得的临床诊断的HP（n = 41）或HNPCC（n = 66），其中具有覆盖着114的编码，侧翼和启动子区域的三种不同的基因面板。癌症预感基因。使用这种方法，我们能够在65/107（60.7％）患者中检测有害突变，其中50.4％在已知良好的CRC易感基因中，DNA修复基因（DRG）中有10.2％。正如预期的那样，在家族性腺瘤性息肉（FAP）和HNPCC患者中检测到有害变体的最高频率，并分别分别为93.8和87.1％的HNPCC患者。在24/107（22.4％）患者中检测到未知意义（VUS）的变体，主要是在HNPCC患者中患有微卫星稳定（MSS）肿瘤或寡替肽患者的患者。大多数VUS也发现在DRG基因中，表明脱卵族制动器DNA修复途径缺乏结直肠癌发生的潜在作用。我们无法检测到18/107（16.8％）患者的任何变体，它支持遗传性CRC的遗传异质性，特别是在HNPCC家族中，含有MSS肿瘤的MSS肿瘤和寡尼痘痘的家族。

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