Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.
Program in Molecular Mechanisms and Experimental Therapy in Oncology (Oncobell), IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.
Hum Mutat. 2019 Nov;40(11):1910-1923. doi: 10.1002/humu.23853. Epub 2019 Jul 29.
Technological advances have allowed the identification of new adenomatous and serrated polyposis genes, and of several candidate genes that require additional supporting evidence of causality. Through an exhaustive literature review and mutational screening of 177 unrelated polyposis patients, we assessed the involvement of MCM9, FOCAD, POLQ, and RNF43 in the predisposition to (nonserrated) colonic polyposis, as well as the prevalence of NTHL1 and MSH3 mutations among genetically unexplained polyposis patients. Our results, together with previously reported data and mutation frequency in controls, indicate that: MCM9 and POLQ mutations are not associated with polyposis; germline RNF43 mutations, with a prevalence of 1.5-2.5% among serrated polyposis patients, do not cause nonserrated polyposis; MSH3 biallelic mutations are highly infrequent among European polyposis patients, and the prevalence of NTHL1 biallelic mutations among unexplained polyposes is ~2%. Although nonsignificant, FOCAD predicted deleterious variants are overrepresented in polyposis patients compared to controls, warranting larger studies to provide definite evidence in favor or against their causal association with polyposis predisposition.
技术进步使得能够鉴定出新的腺瘤性和锯齿状息肉基因，以及几个需要更多因果关系支持证据的候选基因。通过对 177 名无关息肉病患者进行详尽的文献回顾和突变筛选，我们评估了 MCM9、FOCAD、POLQ 和 RNF43 基因在（非锯齿状）结肠息肉易感性中的作用，以及 NTHL1 和 MSH3 基因突变在遗传原因不明的息肉病患者中的发生率。我们的结果，以及之前报道的数据和对照中的突变频率，表明：MCM9 和 POLQ 基因突变与息肉病无关；种系 RNF43 突变，在锯齿状息肉病患者中的发生率为 1.5-2.5%，不会导致非锯齿状息肉病；MSH3 双等位基因突变在欧洲息肉病患者中非常罕见，而在原因不明的息肉病中 NTHL1 双等位基因突变的发生率约为 2%。尽管没有统计学意义，但与对照组相比，FOCAD 预测的有害变异在息肉病患者中更为常见，需要更大的研究来提供明确的证据，支持或反对它们与息肉病易感性的因果关系。
