Mork Maureen E, Rodriguez Andrea, Taggart Melissa W, Rodriguez-Bigas Miguel A, Lynch Patrick M, Bannon Sarah A, You Y Nancy, Vilar Eduardo
Clinical Cancer Genetics Program, UT MD Anderson Center, Unit 1354, 1155 Pressler St., Houston, TX, 77030, USA.
Department of Clinical Cancer Prevention, UT MD Anderson Cancer Center, Unit 1360, P.O. Box 301439, Houston, TX, 77230-1439, USA.
Fam Cancer. 2017 Jul;16(3):357-361. doi: 10.1007/s10689-016-9960-y.
Traditional germline sequencing and deletion/duplication analysis does not detect Lynch syndrome-causing mutations in all individuals whose colorectal or endometrial tumors demonstrate mismatch repair (MMR) deficiency. Unique inversions and other rearrangements of the MMR genes have been reported in families with Lynch syndrome. In 2014, a recurrent inversion of MSH2 exons 1-7 was identified in five families suspected to have Lynch syndrome. We aimed to describe our clinical experience in identifying families with this specific inversion. Four probands whose Lynch syndrome-associated tumors demonstrated absence of MSH2/MSH6 staining and who had negative MMR germline testing were evaluated for the MSH2 inversion of exons 1-7, offered during initial genetic workup or upon routine clinical follow-up. All four probands tested positive for the MSH2 inversion. Proband cancer diagnoses included colon and endometrial adenocarcinoma and sebaceous adenoma. A variety of Lynch syndrome-associated cancers were reported in the family histories, although only one family met Amsterdam II criteria. Thirteen at-risk relatives underwent predictive testing. MSH2 inversion of exons 1-7 was found in four probands previously suspected to have Lynch syndrome based on family history and tumor testing. This testing should be offered routinely to patients with tumors demonstrating loss of MSH2/MSH6 staining.
传统的种系测序和缺失/重复分析并不能在所有结直肠癌或子宫内膜癌表现出错配修复（MMR）缺陷的个体中检测出导致林奇综合征的突变。在林奇综合征家族中已报道了MMR基因的独特倒位和其他重排。2014年，在五个疑似患有林奇综合征的家族中发现了MSH2外显子1-7的反复倒位。我们旨在描述我们在识别具有这种特定倒位的家族中的临床经验。对四名先证者进行了评估，他们的林奇综合征相关肿瘤显示MSH2/MSH6染色缺失且MMR种系检测呈阴性，在初始基因检测或常规临床随访期间对其进行了MSH2外显子1-7倒位检测。所有四名先证者的MSH2倒位检测均呈阳性。先证者的癌症诊断包括结肠癌、子宫内膜腺癌和皮脂腺腺瘤。家族史中报告了多种林奇综合征相关癌症，尽管只有一个家族符合阿姆斯特丹II标准。13名高危亲属接受了预测性检测。在四名先前根据家族史和肿瘤检测疑似患有林奇综合征的先证者中发现了MSH2外显子1-7倒位。对于肿瘤显示MSH2/MSH6染色缺失的患者，应常规进行此项检测。
