Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Genes Chromosomes Cancer. 2021 Aug;60(8):571-576. doi: 10.1002/gcc.22950. Epub 2021 Apr 21.
Germline mutations in the DNA mismatch repair (MMR) genes cause Lynch syndrome (LS). In this study, we identified and characterized a novel SINE-VNTR-Alu (SVA) insertion in exon 12 of MSH2 in an individual with early-onset colorectal cancer and a very strong LS family history. RT-PCR analysis indicated a larger aberrant MSH2 transcript in one of the family members. MSK-IMPACT next-generation sequencing and long-range PCR analyses revealed an insertion in MSH2 exon 12 at the c.1972 position in an antisense orientation. The insertion was further characterized as an SVA element approximately 3 kb in length, belonging to the SVA_F1 family of retrotransposons. This variant also segregated with LS related cancers in four affected family members in this family. Based on this evidence, this MSH2 SVA insertion is considered pathogenic.
DNA 错配修复 (MMR) 基因中的种系突变导致林奇综合征 (LS)。在这项研究中，我们在一名具有早发性结直肠癌和强烈 LS 家族史的个体中鉴定并表征了 MSH2 外显子 12 中的新型 SINE-VNTR-Alu (SVA) 插入。RT-PCR 分析表明，一名家族成员存在更大的异常 MSH2 转录本。MSK-IMPACT 下一代测序和长距离 PCR 分析显示，MSH2 外显子 12 中的插入位于反义方向的 c.1972 位。该插入进一步被表征为大约 3kb 长的 SVA 元件，属于 SVA_F1 家族的逆转录转座子。该变体也与该家族中四名受影响的家族成员中的 LS 相关癌症共分离。基于这一证据，该 MSH2 SVA 插入被认为是致病性的。
