Identification of MSH2 inversion of exons 1-7 in clinical evaluation of families with suspected Lynch syndrome.
Identification of MSH2 inversion of exons 1-7 in clinical evaluation of families with suspected Lynch syndrome.
复制标题
DOI：
10.1007/s10689-016-9960-y
复制
发表时间：
2017-07
期刊：
影响因子：
2.2
通讯作者：
Vilar E
中科院分区：
文献类型：
--
作者：
Mork ME;Rodriguez A;Taggart MW;Rodriguez-Bigas MA;Lynch PM;Bannon SA;You YN;Vilar E
传统的种系测序和缺失/重复分析不能检测出所有结直肠或子宫内膜肿瘤表现出错配修复（MMR）缺陷的个体中导致Lynch综合征的突变。独特的倒位和其他重排的MMR基因已报告在林奇综合征的家庭。2014年，在5个疑似Lynch综合征的家族中发现了MSH 2外显子1-7的复发性倒位。我们的目的是描述我们的临床经验，确定家庭与这种特定的倒位。在初始遗传检查或常规临床随访期间，对4名Lynch综合征相关肿瘤表现为MSH 2/MSH 6染色缺失且MMR生殖系检测阴性的先证者进行MSH 2外显子1-7倒位评价。所有四个先证者的MSH 2倒位检测均为阳性。先证癌症诊断包括结肠和子宫内膜腺癌和皮脂腺腺瘤。在家族史中报告了多种Lynch综合征相关癌症，尽管只有一个家族符合Amsterdam II标准。13名有风险的亲属接受了预测测试。MSH 2外显子1-7的倒位发现在四个先证者先前怀疑有林奇综合征的家族史和肿瘤检测的基础上。该检测应常规提供给肿瘤患者，证明MSH 2/MSH 6染色丢失。
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.