背景:下一代测序允许同时分析强烈怀疑遗传性乳腺癌和/或卵巢癌(HBOC)的家族或个体的大量基因。由于缺乏指导方针,设计了几组可能参与HBOC的基因,不仅在它们的组成上,而且在提供给突变携带者的医疗方面也存在巨大差异。然后,实践中需要同质化。
方法:法国遗传与癌症小组(GGC)-Unicancer对18个感兴趣的基因进行了详尽的书目工作。仅保留具有无偏风险估计的出版物。
结果:每18个基因的专业知识基于临床效用标准,即癌症的相对风险为4或更多,用于筛查和预防突变携带者的可用医疗工具,和亲属的症状前基因测试。最后,13个基因被选择包括在HBOC诊断基因组中:BRCA1,BRCA2,PALB2,TP53,CDH1,PTEN,RAD51C,RAD51D,MLH1、MSH2、MSH6、PMS2、EPCAM。排除NBN的原因,RAD51B,CHEK2,STK11,ATM,介绍了HBOC诊断小组的BARD1、BRIP1。筛选,18个基因中的每一个基因都有详细的预防和遗传咨询指南。
结论:由于知识的迅速增加,GGC计划每年更新参考书目,以考虑新发现。此外,正在启动遗传流行病学研究,以更好地估计与尚未纳入HBOC诊断小组的基因相关的癌症风险.
BACKGROUND: Next generation sequencing allows the simultaneous analysis of large panel of genes for families or individuals with a strong suspicion of hereditary breast and/or ovarian cancer (HBOC). Because of lack of
guidelines, several panels of genes potentially involved in HBOC were designed, with large disparities not only in their composition but also in medical care offered to mutation carriers. Then, homogenization in practices is needed.
METHODS: The French Genetic and Cancer Group (GGC) - Unicancer conducted an exhaustive bibliographic work on 18 genes of interest. Only publications with unbiased risk estimates were retained.
RESULTS: The expertise of each 18 genes was based on clinical utility criteria, i.e. a relative risk of cancer of 4 and more, available medical tools for screening and prevention of mutation carriers, and pre-symptomatic genetic tests for relatives. Finally, 13 genes were selected to be included in a HBOC diagnosis gene panel: BRCA1, BRCA2, PALB2, TP53, CDH1, PTEN, RAD51C, RAD51D, MLH1, MSH2, MSH6, PMS2, EPCAM. The reasons for excluding NBN, RAD51B, CHEK2, STK11, ATM, BARD1, BRIP1 from the HBOC diagnosis panel are presented. Screening, prevention and genetic counselling
guidelines were detailed for each of the 18 genes.
CONCLUSIONS: Due to the rapid increase in knowledge, the GGC has planned a yearly update of the bibliography to take into account new findings. Furthermore, genetic-epidemiological studies are being initiated to better estimate the cancer risk associated with genes which are not yet included in the HBOC diagnosis panel.