European Journal of Medical Genetics ( IF 1.6 ) Pub Date : 2020-10-08 , DOI: 10.1016/j.ejmg.2020.104080 Marion Dhooge , Stéphanie Baert-Desurmont , Carole Corsini , Olivier Caron , Nadine Andrieu , Pascaline Berthet , Valérie Bonadona , Odile Cohen-Haguenauer , Antoine De Pauw , Capucine Delnatte , Sophie Dussart , Christine Lasset , Dominique Leroux , Christine Maugard , Jessica Moretta-Serra , Cornel Popovici , Bruno Buecher , Chrystelle Colas , Catherine Noguès
In case of suspected hereditary predisposition to digestive cancers, next-generation sequencing can analyze simultaneously several genes associated with an increased risk of developing these tumors. Thus, "Gastro Intestinal" (GI) gene panels are commonly used in French molecular genetic laboratories. Lack of international recommendations led to disparities in the composition of these panels and in the management of patients.
To harmonize practices, the Genetics and Cancer Group (GGC)-Unicancer set up a working group who carried out a review of the literature for 31 genes of interest in this context and established a list of genes for which the estimated risks associated with pathogenic variant seemed sufficiently reliable and high for clinical use. Pancreatic cancer susceptibility genes have been excluded.
This expertise defined a panel of 14 genes of confirmed clinical interest and relevant for genetic counseling: APC, BMPR1A, CDH1, EPCAM, MLH1, MSH2, MSH6, MUTYH, PMS2, POLD1, POLE, PTEN, SMAD4 and STK11. The reasons for the exclusion of the others 23 genes have been discussed. The paucity of estimates of the associated tumor risks led to the exclusion of genes, in particular CTNNA1, MSH3 and NTHL1, despite their implication in the molecular pathways involved in the pathophysiology of GI cancers.
A regular update of the literature is planned to up-grade this panel of genes in case of new data on candidate genes. Genetic and epidemiological studies and international collaborations are needed to better estimate the risks associated with the pathogenic variants of these genes either selected or not in the current panel.
中文翻译:
法国遗传与癌症小组的国家建议-Unicancer关于遗传性消化道肿瘤易感性的多基因面板分析的方法
在怀疑遗传性易消化性癌症的情况下,下一代测序可以同时分析与罹患这些肿瘤的风险增加相关的几个基因。因此,“胃肠道”(GI)基因面板常用于法国分子遗传实验室。缺乏国际建议导致这些小组的组成和患者管理方面的差异。
为了协调实践,遗传和癌症小组(GGC)-Unicancer成立了一个工作小组,负责对这种情况下31种感兴趣基因的文献进行回顾,并确定了与致病变异相关的估计风险的基因清单似乎足够可靠并且对于临床使用而言很高。胰腺癌易感基因已被排除。
该专业知识定义了一组14个已确认具有临床意义且与遗传咨询相关的基因:APC,BMPR1A,CDH1,EPCAM,MLH1,MSH2,MSH6,MUTYH,PMS2,POLD1,POLE,PTEN,SMAD4和STK11。讨论了排除其他23个基因的原因。尽管缺乏相关基因风险的估计,导致基因特别是CTNNA1,MSH3和NTHL1被排除在外,尽管它们涉及胃肠道癌的病理生理学涉及的分子途径。
计划定期更新文献,以在候选基因有新数据的情况下升级该基因组。需要进行遗传和流行病学研究以及国际合作才能更好地估计与当前小组中选择或未选择的这些基因的致病性变体相关的风险。