Precision Medicine, School of Clinical Science at Monash Health, Monash University Clayton, Melbourne, VIC, 3168, Australia.
Department of Clinical Pathology, The University of Melbourne, Melbourne, VIC, 3010, Australia.
Fam Cancer. 2020 Jul;19(3):197-202. doi: 10.1007/s10689-020-00164-7.
The advent of gene panel testing is challenging the previous practice of using clinically defined cancer family syndromes to inform single-gene genetic screening. Individual and family cancer histories that would have previously indicated testing of a single gene or a small number of related genes are now, increasingly, leading to screening across gene panels that contain larger numbers of genes. We have applied a gene panel test that included four DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6 and PMS2) to an Australian population-based case-control-family study of breast cancer. Altogether, eight pathogenic variants in MMR genes were identified: six in 1421 case-families (0.4%, 4 MSH6 and 2 PMS2) and two in 833 control-families (0.2%, one each of MLH1 and MSH2). This testing highlights the current and future challenges for clinical genetics in the context of anticipated gene panel-based population-based screening that includes the MMR genes. This testing is likely to provide additional opportunities for cancer prevention via cascade testing for Lynch syndrome and precision medicine for breast cancer treatment.
基因面板检测的出现，挑战了以往利用临床定义的癌症家族综合征来指导单基因遗传筛查的做法。以前，个人和家族的癌症病史表明需要对单个基因或少数相关基因进行检测，而现在，越来越多的情况是对包含更多基因的基因面板进行筛查。我们对一个基于澳大利亚人群的乳腺癌病例对照家族研究应用了一种包含四个 DNA 错配修复 (MMR) 基因 (MLH1、MSH2、MSH6 和 PMS2) 的基因面板检测。总共在 1421 个病例家族（0.4%，4 个 MSH6 和 2 个 PMS2）和 833 个对照家族（0.2%，各有一个 MLH1 和 MSH2）中发现了 8 种致病性 MMR 基因突变。这种检测强调了在预期基于基因面板的人群筛查（包括 MMR 基因）的背景下，临床遗传学当前和未来的挑战。这种检测可能为林奇综合征的级联检测和乳腺癌治疗的精准医学提供更多的癌症预防机会。
