Akbari Mohammad R, Zhang Shiyu, Cragun Deborah, Lee Ji-Hyun, Coppola Domenico, McLaughlin John, Risch Harvey A, Rosen Barry, Shaw Patricia, Sellers Thomas A, Schildkraut Joellen, Narod Steven A, Pal Tuya
Women's College Research Institute, Women's College Hospital, University of Toronto, 790 Bay Street, 7th Floor, Toronto, ON, M5G 1N8, Canada.
Departments of Cancer Epidemiology, Moffitt Cancer Center, Biostatistics, Anatomic Pathology, and Experimental Therapeutics, 12902 Magnolia Drive, Tampa, FL, 33612, USA.
Fam Cancer. 2017 Jul;16(3):351-355. doi: 10.1007/s10689-017-9973-1.
A high proportion of ovarian cancers from women who carry germline mutations in mismatch repair (MMR) genes demonstrate microsatellite instability (MSI). The utility of pre-screening ovarian cancer specimens for MSI to identify potential patients for germline screening for MMR mutations is uncertain. 656 women with malignant ovarian cancer underwent both MSI testing and germline mutation testing for large rearrangements in three MMR genes, MLH1, MSH2 and MSH6. Germline DNA sequencing data for the same genes was available. Among the 656 women, only four (0.6%) carried a clearly pathogenic MMR mutation. All four cancers from patients with mutations had loss of two or more microsatellite markers (MSI-high). Eighty-four of 652 (13.0%) women without a mutation had MSI-high ovarian cancers. Using MSI-high as a prescreening criterion, the sensitivity of MSI testing to identify germline MMR gene mutations was 100% and the positive predictive value was 4.5%. Germline mutations in MLH1, MSH2 and MSH6 are rare among unselected cases of ovarian cancer. Patients with germline mutations often will have MSI-positive cancers and pre-screening of ovarian cancer specimens may be an efficient way of identifying patients with Lynch syndrome.
在携带错配修复（MMR）基因种系突变的女性中，很大一部分卵巢癌表现出微卫星不稳定性（MSI）。对卵巢癌标本进行MSI预筛查以确定可能进行MMR突变种系筛查的患者，其效用尚不确定。656例患有恶性卵巢癌的女性接受了MSI检测以及对三个MMR基因（MLH1、MSH2和MSH6）的大片段重排进行种系突变检测。同时可获得相同基因的种系DNA测序数据。在这656名女性中，只有4名（0.6%）携带明确的致病性MMR突变。所有来自有突变患者的癌症均有两个或更多微卫星标记缺失（MSI高）。652名无突变的女性中有84名（13.0%）患有MSI高的卵巢癌。以MSI高作为预筛查标准，MSI检测识别种系MMR基因突变的敏感性为100%，阳性预测值为4.5%。在未经选择的卵巢癌病例中，MLH1、MSH2和MSH6的种系突变很少见。有种系突变的患者通常会患有MSI阳性癌症，对卵巢癌标本进行预筛查可能是识别林奇综合征患者的有效方法。
