Data_Sheet_1_Case Report: A New Subtype of Lynch Syndrome Associated With MSH2 c.1024_1026 Identified in a Chinese Family.docx

BackgroundLynch syndrome is an autosomal dominant disorder associated with a high incidence of various cancer types. Multiple variants of mismatch repair genes have been reported for Lynch syndrome. However, the diagnosis in patients with atypical cancer types remains challenging. Specifically, little is known about the genetic background of Lynch syndrome-related renal carcinoma. We present a case wherein a renal carcinoma patient with multiple primary skin tumors harbored a variant that has not been previously shown to be associated with Lynch syndrome.Case PresentationThe proband was a 60-year-old Chinese man with a history of Lynch syndrome-related renal carcinoma and recurrent primary skin tumors. Immunohistochemistry revealed loss of MSH2 and MSH6. Sequencing of mismatch repair genes revealed a previously unknown germline MSH2 mutation (c.1024_1026), which results in an amino acid deletion (p.V342). This variant was co-segregated among the carcinoma-affected family members. After six cycles of immunotherapy, a marked regression of the skin tumors was observed.ConclusionsWe clarify the pathogenic significance of this newly described mutation and suggest immunotherapy for patients with this subtype of Lynch syndrome.

背景：林奇综合征是一种常染色体显性遗传性疾病，其特征为多种癌症类型的高发病率。关于林奇综合征的不匹配修复基因已报道有多种变异。然而，对于不典型癌症类型的患者，诊断仍然具有挑战性。特别是，关于林奇综合征相关肾细胞癌的遗传背景知之甚少。本研究报道了一例肾细胞癌患者，该患者伴有多个原发性皮肤肿瘤，并携带一种先前未发现与林奇综合征相关的变异。病例报告：受试者为一名60岁的中国男性，既往有林奇综合征相关肾细胞癌和复发性原发性皮肤肿瘤病史。免疫组化检测显示MSH2和MSH6蛋白表达缺失。不匹配修复基因测序发现了一种先前未知的胚系MSH2突变（c.1024_1026），导致氨基酸缺失（p.V342）。该变异在受影响的肿瘤家族成员中共同分离。经过六周期的免疫治疗后，皮肤肿瘤明显消退。结论：我们阐明了该新描述的突变致病学意义，并建议对林奇综合征此亚型的患者进行免疫治疗。