Molecular and clinical characteristics of glioma patients with germline pathogenic mutations of Lynch syndrome genes - a largescale multicenter study

Sep 22, 2026

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Lynch syndrome (LS) is an inherited mismatch repair disorder linked to gastrointestinal and endometrial cancer risk, yet LS-associated gliomas remain rare with poorly defined clinical and molecular traits. This large-scale multicenter retrospective study evaluates the prevalence, genetic landscape, molecular features, and clinical outcomes of LS-associated gliomas using targeted next-generation sequencing in 5,594 glioma patients and compares findings with LS-associated colorectal cancer cohorts.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Abstract

Background

Methods

Results

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Introduction

Feng et al. Journal of Translational Medicine (2026) 24:711 [https://doi.org/10.1186/s12967-026-08119-9](https://doi.org/10.1186/s12967-026-08119-9) Journal of Translational Medicine RESEARCH Open Access Molecular and clinical characteristics of glioma patients with germline pathogenic mutations of Lynch syndrome genes: a largescale multicenter study Jiao Feng1,2†, Tonghui Ma3,4†, Xiang Zhang4†, Yi Zhang5†, Zhenyuan Qian1†, Yuxiang Dai6, Zhixian Gao7, Rui Zhao8, Chengjun Yao5, Guhong Du5, Naiyuan Shao9, Zhen Wu7, Nan Ji7, Jia Gu10, Zhengchuan Liu1, Qiong Yang11, Xiaochen Sun2, Wei Li4, Xiaomo Li4, Yanxiang Zhang4*, Zaiyuan Ye1* and Anchao Yang7* Abstract Background Lynch syndrome (LS) is an inherited disorder caused by germline mutations in mismatch repair (MMR) genes or EPCAM deletions and is primarily associated with an increased risk of gastrointestinal and endometrial cancers. However, LS-associated gliomas are rare, and their clinical and molecular characteristics remain poorly defined. The objective of this study was to systematically characterize the prevalence, genetic landscape, molecular features, and clinical outcomes of LS-associated gliomas. Methods We retrospectively analyzed a multicenter cohort of 5,594 glioma patients who underwent targeted nextgeneration sequencing to identify pathogenic germline mutations in LS-associated genes. Clinical characteristics, molecular features, treatment histories, and outcomes of LS-associated glioma patients were systematically evaluated and compared with those of LS-associated colorectal cancer (CRC) patients. Results Among 5,594 glioma patients, 54 individuals (0 . 97%) were identified as carrying pathogenic germline LS-associated mutations, with a median age of 37.9 years. High-grade gliomas accounted for 68 . 5%(37/54) of cases, while 9 . 3%(5/54) were low-grade gliomas. Mutations in MSH2 and MSH6 were predominant, showing a distribution distinct from that observed in LS-associated colorectal cancer (CRC) . Compared with LS CRC patients, LS-associated glioma patients exhibited significantly lower frequencies of high tumor mutational burden (TMB-H), microsatellite instability–high (MSI-H), and PD-L1 positivity, indicating unique molecular characteristics. Treatment history analysis †Jiao Feng, Tonghui Ma, Xiang Zhang, Yi Zhang and Zhenyuan Qian contributed equally to this work. *Correspondence: Yanxiang Zhang [yxzhang2008@hotmail.com](yxzhang2008@hotmail.com)[ ](yxzhang2008@hotmail.com)Zaiyuan Ye [zaiyuanye@163.com](zaiyuanye@163.com)[ ](zaiyuanye@163.com)Anchao Yang [yang.anchao@163.com](yang.anchao@163.com) Full list of author information is available at the end of the article © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creati](http://creati)[vecommons.org/licenses/by-nc-nd/4.0/](vecommons.org/licenses/by-nc-nd/4.0/.)[.](vecommons.org/licenses/by-nc-nd/4.0/.) Feng et al. Journal of Translational Medicine (2026) 24:711 Page 2 of 14 showed that LS glioma patients generally responded well to temozolo

FAQs

What was the main objective of the study on LS-associated gliomas?

To systematically characterize the prevalence, genetic landscape, molecular features, and clinical outcomes of LS-associated gliomas.

How were LS-associated glioma patients identified in the study?

Researchers retrospectively analyzed a multicenter cohort of 5,594 glioma patients using targeted next-generation sequencing to detect pathogenic germline mutations in LS-associated genes.

What did the study find about treatment response and prognosis?

LS glioma patients generally responded well to temozolomide, but those carrying MSH2 mutations had a worse prognosis.

Sep 22, 2026

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