New York University Grossman School of Medicine, New York, NY, USA.
Moffitt Cancer Center, Tampa, FL, USA.
Gynecol Oncol. 2022 Jun;165(3):546-551. doi: 10.1016/j.ygyno.2022.04.003. Epub 2022 Apr 26.
Patients with germline mutations in mismatch repair genes (MLH1, MSH2, MSH6, PMS2) associated with Lynch syndrome (LS) have an increased lifetime risk of endometrial cancer (EC). Multi-gene panel testing (MGPT) is a recent hereditary cancer risk tool enabling next-generation sequencing of numerous genes in parallel. We determined the prevalence of actionable cancer predisposition gene mutations identified through MGPT in an EC patient cohort.
A single center retrospective cohort study was conducted of patients with EC who had a clinical indication for genetic testing and who underwent MGPT as part of standard of care treatment between 2012 and 2021. Pathogenic mutations were identified and actionable mutations were defined as those with clinical management implications. Additionally, the number of individuals identified with LS was compared between MGPT and tumor-based screening.
The study included a total of 224 patients. Thirty-three patients [14.7%, 95% confidence interval (CI) = 10.4-20.1] had actionable mutations. Twenty-one patients (9.4%, 95% CI = 5.9-14.0) had mutations in LS genes (4 MLH1, 5 MSH2, 7 MSH6, 4 PMS2, 1 Epcam-MSH2). MGPT revealed two patients with LS (9.5% of LS cases) not identified through routine tumor-based screening. Thirteen patients (5.8%, 95% CI = 3.1-9.7) had at least one actionable mutation in a non-Lynch syndrome gene (6 CHEK2, 2 BRCA2, 2 ATM, 2 APC, 1 RAD51C, 1 BRCA1).
Germline MGPT is both feasible and informative as it identifies LS cases not found on tumor testing as well as additional actionable mutations in patients with EC.
与林奇综合征（LS）相关的错配修复基因（MLH1、MSH2、MSH6、PMS2）种系突变的患者终生患子宫内膜癌（EC）的风险增加。多基因panel 检测（MGPT）是一种最近的遗传性癌症风险工具，可实现众多基因的下一代测序并行。我们确定了在 EC 患者队列中通过 MGPT 识别的可操作的癌症易感性基因突变的患病率。
对 2012 年至 2021 年间因临床需要进行基因检测且作为标准治疗一部分接受 MGPT 的 EC 患者进行了一项单中心回顾性队列研究。确定了致病性突变，并将具有临床管理意义的突变定义为可操作的突变。此外，还比较了 MGPT 和基于肿瘤的筛查之间识别 LS 个体的数量。
该研究共纳入 224 例患者。33 例患者（14.7%，95%置信区间 [CI] = 10.4-20.1）存在可操作的突变。21 例（9.4%，95% CI = 5.9-14.0）患者存在 LS 基因（4 例 MLH1、5 例 MSH2、7 例 MSH6、4 例 PMS2、1 例 Epcam-MSH2）突变。MGPT 发现了 2 例通过常规基于肿瘤的筛查未发现的 LS 患者（LS 病例的 9.5%）。13 例患者（5.8%，95% CI = 3.1-9.7）至少有一种非林奇综合征基因的可操作突变（6 例 CHEK2、2 例 BRCA2、2 例 ATM、2 例 APC、1 例 RAD51C、1 例 BRCA1）。
MGPT 既可行又有信息性，因为它不仅可以识别肿瘤检测中未发现的 LS 病例，还可以识别 EC 患者的其他可操作突变。
