微卫星不稳定性高胃癌患者错配修复基因的致病种系变异。

IF 7 2区 医学 Q1 ONCOLOGY
Jong Hyuk Yun, Geum Jong Song, In Cho, Sangchul Yun, Myoung Won Son, Sang Hyun Kim, Moon-Soo Lee, Yoon Young Choi
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引用次数: 0

摘要

目的:Lynch综合征(LS)可增加结直肠癌、子宫内膜癌和胃癌(GC)等多种癌症的发病风险。在韩国,LS在微卫星不稳定高(MSI-H) GC中的发病率及其相关性仍未得到充分探讨。本研究利用正常组织的全外显子组测序(WES)研究了MSI-H GC患者中ls相关的致病种系变异。方法:本回顾性研究纳入2011年1月至2023年10月在顺春乡大学富川医院和天安医院接受胃切除术的胃癌患者。在1537例MSI状态筛查患者中,127例(8.3%)被确定为MSI- h。对123例患者的正常组织进行WES检查。利用计算机模型和相应肿瘤组织的蛋白质损失评估,鉴定错配修复(MMR)基因的致病性/可能致病性(P/LP)变异。结果:127例MSI-H GC病例的特征符合典型的MSI-H GC。平均年龄70.02岁,其中下体98例(77.2%),肠型81例(63.8%)。46.5%的病例5项MSI指标均为阳性,而27.6%的病例4项指标均为阳性。在MSI-H gc中,确定了10个LS候选物。3例患者有已知的P/LP变异[MLH1 (C .1758dup), MSH6 (C .3261dup), MSH2 (C . 1241t> C)]。7例患者MMR基因存在未知意义变异(VUS)。6例(4.9%)患者被确定为LS或可能的LS,包括1例MLH1 (c.1153C>T)变异患者,先前被归类为VUS,但现在被认为与LS相关。结论:通过回顾性样本对MSI-H胃癌患者LS进行大规模筛查,证实了LS的发生率低于西方国家结直肠癌或子宫内膜癌及胃癌患者,强调了MSI-H胃癌患者的管理需要临床考虑。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pathogenic germline variants in mismatch repair genes in patients with microsatellite instability-high gastric cancer.

Objective: Lynch syndrome (LS) increases the risk of various cancers, including colorectal cancer, endometrial cancer and gastric cancer (GC). The incidence of LS among microsatellite instability-high (MSI-H) GC and their association in South Korea remains underexplored. This study investigates LS-associated pathogenic germline variants in MSI-H GC patients using whole-exome sequencing (WES) on normal tissues.

Methods: This retrospective study included patients who underwent gastrectomy for GC at Soonchunhyang University Bucheon and Cheonan Hospitals from January 2011 to October 2023. Among 1,537 patients screened for MSI status, 127 (8.3%) were identified as MSI-H. WES was performed on normal tissues from 123 patients. Pathogenic/likely pathogenic (P/LP) variants in mismatch repair (MMR) genes were identified using in silico models and protein loss assessments in corresponding tumor tissues.

Results: Of the 127 MSI-H GC cases, characteristics aligned with typical MSI-H GC. The average age was 70.02 years, with 98 (77.2%) located in the lower body and 81 (63.8%) of the intestinal type. All five MSI markers were positive in 46.5% of cases, whereas four markers were positive in 27.6%. Of the MSI-H GCs, 10 LS candidates were identified. Three patients had known P/LP variants [MLH1 (c.1758dup), MSH6 (c.3261dup), MSH2 (c.1241T>C)]. Seven patients had variants of unknown significance (VUS) in MMR genes. Six (4.9%) patients were identified as having LS or possible LS, including one patient with the MLH1 (c.1153C>T) variant previously classified as VUS but now considered LS-associated.

Conclusions: This large-scale screening for LS in MSI-H GC patients using retrospective samples confirmed the lower incidence of LS than those of colorectal or endometrial cancer and GC patients in Western countries, emphasizing the need for clinical consideration in managing MSI-H GC patients.

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来源期刊
自引率
9.80%
发文量
1726
审稿时长
4.5 months
期刊介绍: Chinese Journal of Cancer Research (CJCR; Print ISSN: 1000-9604; Online ISSN:1993-0631) is published by AME Publishing Company in association with Chinese Anti-Cancer Association.It was launched in March 1995 as a quarterly publication and is now published bi-monthly since February 2013. CJCR is published bi-monthly in English, and is an international journal devoted to the life sciences and medical sciences. It publishes peer-reviewed original articles of basic investigations and clinical observations, reviews and brief communications providing a forum for the recent experimental and clinical advances in cancer research. This journal is indexed in Science Citation Index Expanded (SCIE), PubMed/PubMed Central (PMC), Scopus, SciSearch, Chemistry Abstracts (CA), the Excerpta Medica/EMBASE, Chinainfo, CNKI, CSCI, etc.
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