Supplementary Fig. S14 from Genomic Analyses Reveal the Evolving Characteristics of Intestinal Metaplasia and Gastric Cancer

Xu, Xianfeng; Yan, Caiwang; Bian, Lijun; Li, Zhe; Yu, Yuhui; Zhu, Xia; Gao, Yun; Xu, Hao; Li, Fengyuan; Liu, Yao; Sun, Ping; Wang, Zheng; Fu, Yao; Jiang, Yue; Dai, Juncheng; Ma, Hongxia; Hu, Zhibin; Shen, Hongbing; Li, Gang; Wang, Cheng; Jin, Guangfu

doi:10.1158/0008-5472.29919198

Supplementary Fig. S14 from Genomic Analyses Reveal the Evolving Characteristics of Intestinal Metaplasia and Gastric Cancer

journal contribution

posted on 2025-08-15, 08:21 authored by Xianfeng Xu, Caiwang Yan, Lijun Bian, Zhe Li, Yuhui Yu, Xia Zhu, Yun Gao, Hao Xu, Fengyuan Li, Yao Liu, Ping Sun, Zheng Wang, Yao Fu, Yue Jiang, Juncheng Dai, Hongxia Ma, Zhibin Hu, Hongbing Shen, Gang Li, Cheng Wang, Guangfu Jin

<p>Association between TP53 and CDH1 mutations and mutation burden in GC.</p>

Funding

National Natural Science Foundation of China (NSFC)

Outstanding Youth Foundation of Jiangsu Province (Outstanding Youth Foundation of Jiangsu Province of China)

Jiangsu Cancer Hospital (江苏省肿瘤医院)

Nanjing Medical University (NMU)

History

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DOI - Is supplement to Genomic Analyses Reveal the Evolving Characteristics of Intestinal Metaplasia and Gastric Cancer

ARTICLE ABSTRACT

Intestinal metaplasia (IM) represents a precancerous condition associated with an increased risk of gastric cancer. A better understanding of whether and how precancerous lesions progress to gastric cancer is crucial for patient stratification and personalized prevention. In this study, we reconstruct evolutionary trajectories of genomic alterations in 330 multiregion matched samples of IM and tumors from 93 patients with gastric cancer. Intestinal-type gastric cancer (IGC) exhibited a higher mutation burden than diffuse-type gastric cancer (DGC), notably in genomically stable patients. IM from genomically stable patients carried more mutations associated with alcohol consumption. The 20 significantly mutated genes identified were classified into three evolutionary patterns. “Maintained” genes (TP53, APC, and PIK3CA) were commonly altered in IM and matched gastric cancer samples in both IGC and DGC, whereas CDH1 mutations were specific to DGC. “Maintained” mutations in IM accelerated gastric cancer progression. Alterations in “IM-favored” genes (MUC6, CFTR, BMP6, and MTRR) were associated with IM development but were negatively selected in gastric cancer. Interestingly, MUC6 mutations were enriched in specific pit cells with upregulation of GKN1 and GKN2. The remaining genes were “gastric cancer–favored” and showed high heterogeneity in gastric cancer. These findings illuminate the genomic evolution from IM to IGC or DGC, providing insights that could guide precancerous lesion surveillance and early prevention strategies. Comprehensive genomic characterization uncovers maintained and gained alterations during evolution from intestinal metaplasia to gastric cancer, which could serve as predictive biomarkers to identify individuals at high risk of developing cancer.