Background: Hereditary polyposis syndromes are clinically and genetically heterogeneous conditions associated with increased colorectal cancer risk. They are classified based on polyp histology, inheritance mode, causal gene, and colonic and extracolonic manifestations. Their diagnosis is challenging due to overlapping and heterogeneous clinical presentations.Methods: A multigene next-generation sequencing panel was used to screen 75 index cases with colorectal polyps and a personal/family history of cancer for key hereditary polyposis-associated genes (APC,BMPR1A,MUTYH,PTEN,SMAD4, andSTK11) in order to identify germline genetic variants.Results: In the screened index cases, we found 14 pathogenic variants involvingAPC,MUTYH,SMAD4, andSTK11and 6 variants of uncertain significance involvingAPC,BMPR1A, andSMAD4. In this cohort, four patients not fulfilling the recommended eligibility criteria of current National Comprehensive Cancer Network (NCCN) guidelines for genetic testing were molecularly diagnosed with a hereditary polyposis syndrome.Conclusions: Our findings indicate that stringent NCCN eligibility criteria for molecular screening may lead to missing some of the patients affected by hereditary polyposis syndromes. This highlights the need for a careful evaluation of patients’ clinical manifestations, polyp number, age of polyp onset, and family history to select appropriate candidates for molecular diagnosis of these conditions.
背景：遗传性息肉病综合征是一类临床与遗传学上均具有异质性的疾病，与结直肠癌风险升高相关。其分类依据包括息肉组织学特征、遗传模式、致病基因以及结肠内外的临床表现。由于临床表现存在重叠性和异质性，其诊断颇具挑战性。 方法：本研究采用多基因二代测序组合，对75例具有结直肠息肉及个人/家族癌症史的先证者进行了关键遗传性息肉病相关基因（APC、BMPR1A、MUTYH、PTEN、SMAD4和STK11）的筛查，以识别胚系遗传变异。 结果：在筛查的先证者中，我们发现了14个涉及APC、MUTYH、SMAD4和STK11的致病性变异，以及6个涉及APC、BMPR1A和SMAD4的意义未明变异。在本队列中，有四名不符合当前美国国家综合癌症网络（NCCN）指南建议的基因检测资格标准的患者，通过分子诊断被确诊为遗传性息肉病综合征。 结论：我们的研究结果表明，严格的NCCN分子筛查资格标准可能导致遗漏部分遗传性息肉病综合征患者。这凸显了需要仔细评估患者的临床表现、息肉数量、息肉发病年龄及家族史，以选择合适的对象进行此类疾病的分子诊断。
肿瘤(癌症)患者之家