Germline multi-gene hereditary cancer panel testing in an unselected endometrial cancer cohort.
Germline multi-gene hereditary cancer panel testing in an unselected endometrial cancer cohort.
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DOI：
10.1038/modpathol.2016.135
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发表时间：
2016-11
期刊：
影响因子：
--
通讯作者：
Broaddus RR
中科院分区：
文献类型：
--
作者：
Ring KL;Bruegl AS;Allen BA;Elkin EP;Singh N;Hartman AR;Daniels MS;Broaddus RR
遗传性子宫内膜癌与Lynch综合征基因的生殖系突变有关其他癌症易感基因的作用尚不清楚。我们的目的是确定子宫内膜癌患者队列中癌症易感基因突变的患病率。使用基于下一代测序的面板，在381名子宫内膜癌患者中鉴定了25个基因的突变，这些患者接受了肿瘤检测以筛查Lynch综合征。35例患者（9.2%）有有害突变：22例（5.8%）在Lynch综合征基因中（3例MLH 1，5例MSH 2，2例EPCAM-MSH 2，6例MSH 6，6例PMS 2），13例（3.4%）在10个非Lynch综合征基因中（4例CHEK 2，APC，ATM，BARD 1，BRCA 1，BRCA 2，BRIP 1，NBN，PTEN，RAD 51 C各1例）。在21例Lynch综合征基因有害突变的患者中，2例（9.5%）的肿瘤检测结果提示散发性癌症。在MSH 6和PMS 2中具有有害突变的12名患者中，10名在>50岁时被诊断，8名没有Lynch综合征相关癌症的家族史。在非Lynch综合征基因中有有害突变的患者更可能具有浆液性肿瘤组织学（23.1% v6.4%，p=0.02）。3例非Lynch综合征有害突变和浆液性组织学的患者在BRCA 2、BRIP 1和RAD 51 C中存在突变。目前的临床标准未能识别Lynch综合征和其他遗传性癌症综合征中的一部分可操作突变。肿瘤检测的性能特征足够稳健，可实施通用肿瘤检测以识别Lynch综合征患者。生殖系多基因面板测试是可行的和信息丰富的，导致额外的可操作的突变的鉴定。
Hereditary endometrial carcinoma is associated with germline mutations in Lynch syndrome genes. The role of other cancer predisposition genes is unclear. We aimed to determine the prevalence of cancer predisposition gene mutations in an unselected endometrial carcinoma patient cohort. Mutations in 25 genes were identified using a next generation sequencing based panel applied in 381 endometrial carcinoma patients who had undergone tumor testing to screen for Lynch syndrome. Thirty five patients (9.2%) had a deleterious mutation: 22 (5.8%) in Lynch syndrome genes (3 MLH1, 5 MSH2, 2 EPCAM-MSH2, 6 MSH6, 6 PMS2) and 13 (3.4%) in 10 non-Lynch syndrome genes (4 CHEK2, 1 each in APC, ATM, BARD1, BRCA1, BRCA2, BRIP1, NBN, PTEN, RAD51C). Of 21 patients with deleterious mutations in Lynch syndrome genes with tumor testing, 2 (9.5%) had tumor testing results suggestive of sporadic cancer. Of 12 patients with deleterious mutations in MSH6 and PMS2, 10 were diagnosed at age >50 and 8 did not have a family history of Lynch syndrome associated cancers. Patients with deleterious mutations in non-Lynch syndrome genes were more likely to have serous tumor histology (23.1% v 6.4%, p=0.02). The 3 patients with non-Lynch syndrome deleterious mutations and serous histology had mutations in BRCA2, BRIP1, and RAD51C. Current clinical criteria fail to identify a portion of actionable mutations in Lynch syndrome and other hereditary cancer syndromes. Performance characteristics of tumor testing are sufficiently robust to implement universal tumor testing to identify patients with Lynch syndrome. Germline multi-gene panel testing is feasible and informative, leading to the identification of additional actionable mutations.
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影响因子：
3.3
作者：
Bruegl, Amanda S.;Djordjevic, Bojana;Broaddus, Russell R.
通讯作者：
Broaddus, Russell R.
影响因子：
29.4
作者：
Haraldsdottir S;Hampel H;Tomsic J;Frankel WL;Pearlman R;de la Chapelle A;Pritchard CC
通讯作者：
Pritchard CC
影响因子：
7.3
作者：
Geurts-Giele, Willemina R. R.;Leenen, Celine H. M.;Dinjens, Winand N. M.
通讯作者：
Dinjens, Winand N. M.
影响因子：
4.7
作者：
Lancaster, Johnathan M.;Powell, C. Bethan;Herzog, Thomas J.
通讯作者：
Herzog, Thomas J.
影响因子：
1.5
作者：
Backes, Floor J.;Cohn, David E.
通讯作者：
Cohn, David E.