WGS identifies Lynch syndrome (LS) patients and uncovers a large family with MSH2-related LS in Southern Thailand

Sep 22, 2026

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This study investigates Lynch Syndrome (LS)-related germline variants among Southern Thai colorectal cancer (CRC) patients and other LS-associated cancer patients meeting revised Bethesda guidelines. Whole genome sequencing was performed on 132 probands, identifying 11 germline variants in 26 individuals (20%), including pathogenic, likely pathogenic, and uncertain significance variants in mismatch repair genes. MSH2 c.1237C>T segregated across a shared ancestry, and targeted sequencing added carriers. Cost-effectiveness analysis supported genetic testing over endoscopic surveillance, emphasizing screening, counseling, and tailored surveillance in high-risk families.

LanguageEnglish

CategoryResearch & Report

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Pages18

Reading Time45 min

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Abstract

Introduction

OPEN ACCESS Citation: Wanitsuwan W, Kanjanapradit K, Jearanai S, Suphasynth Y, Supaattagorn P, Vijasika S, et al. (2026) WGS identifies Lynch syndrome (LS) patients and uncovers a large family with MSH2-related LS in Southern Thailand. PLoS One 21(5): e0348867. [https://](https://)[ ](https://)[doi.org/10.1371/journal.pone.0348867](doi.org/10.1371/journal.pone.0348867) Editor: Peh Yean Cheah, Singapore General Hospital, SINGAPORE Received: July 18, 2025 Accepted: April 22, 2026 Published: May 11, 2026 Copyright: © 2026 Wanitsuwan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data availability statement: All relevant data are within the paper and its Supporting information files. Funding: This project was supported by a grant from the Health Systems Research Institute (HSRI) in partnership with Genomics Thailand RESEARCH ARTICLE WGS identifies Lynch syndrome (LS) patients and uncovers a large family with MSH2-related LS in Southern Thailand Worrawit Wanitsuwan1, Kanet Kanjanapradit2, Supakool Jearanai1, Yuthasak Suphasynth3, Pongsatorn Supaattagorn4, Sukanya Vijasika2, Surasak Wanram5, Chumpol Ngamphiw6, Vorthunju Nakhonsri6, Sissades Tongsima6, Palakorn Satsue7, Natnaree Sangkeaw1, Sukanya Horpaopan8* 1 Department of Surgery, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand, 2 Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand, 3 Department of Obstetrics and Gynecology, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand, 4 Ubon Ratchathani Cancer Hospital, Ubon Ratchathani, Thailand, 5 College of Medicine and Public Health, Ubon Ratchathani University, Ubon Ratchathani, Thailand, 6 Medical Molecular Biotechnology Research Group, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Pathum Thani, Thailand, 7 Faculty of Economics, Prince of Songkla University, Songkhla, Thailand, 8 Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand * [sukanya.horpaopan@cmu.ac.th](sukanya.horpaopan@cmu.ac.th) Abstract This study aimed to investigate Lynch Syndrome (LS)-related germline variants among Southern Thai patients with colorectal cancer (CRC) and other LS-associated cancers who met the revised Bethesda guidelines. A total of 132 probands suspected of LS underwent whole genome sequencing (WGS) . Eleven germline variants including pathogenic variants (PVs), likely pathogenic variants (LPVs), and potential variants of uncertain significance (VUSs) in DNA mismatch repair (MMR) genes were identified in twenty-six individuals (20%) . Among these, six PVs/LPVs/VUSs were detected in MLH1 , three in MSH2 , and two in PMS2 . Notably, the MSH2 c. 1237C >T PV was detected in ten probands who were determined to share a common ancestry. Subsequent targeted sequencing of 56 relatives revealed fifteen additional carriers, four had already developed CRC or ampullary cancer, while colonoscopy surveillance detected polyps in two others. The benefit-cost ratio (BCR) analysis demonstrated the greater cost-effectiveness of genetic testing compared to endoscopic surveillance to all relatives at risk. Although our cohort is clinically enriched and does not reflect the population prevalence of LS in Southern Thailand, these findings highlight the substantial LS burden within high-risk families and underscore the importance of incorporating genetic screening, counseling, and tailored surveillance strategies into clinical practice. PLOS One | [https://doi.org/10.1371/journal.pone.0348867](https://doi.org/10.1371/journal.pone.0348867) May 11, 2026 1 / 18 (Grant ID: 64-114, 65-064, and 66-155) . The funders had no role in study design, data collection and an

FAQs

What was the main objective of the study?

To investigate Lynch Syndrome (LS)-related germline variants among Southern Thai patients with colorectal cancer and other LS-associated cancers who met revised Bethesda guidelines.

How were suspected LS probands evaluated?

A total of 132 probands underwent whole genome sequencing (WGS) to identify germline variants in DNA mismatch repair genes.

What did the study find about MSH2-related LS in the family?

The MSH2 c.1237C>T pathogenic variant was detected in ten probands sharing a common ancestry, and subsequent targeted sequencing identified additional carriers among relatives.

Sep 22, 2026

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