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Updated: Oct 15, 2025
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Mapping the genomic diaspora of gastric cancer
Khay Guan Yeoh1,2,3, Patrick Tan4,5,6,7
1Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Abstract:
Gastric cancer (GC) is a leading contributor to global cancer incidence and mortality. Pioneering genomic studies, focusing largely on primary GCs, revealed driver alterations in genes such as ERBB2, FGFR2, TP53 and ARID1A as well as multiple molecular subtypes. However, clinical efforts targeting these alterations have produced variable results, hampered by complex co-alteration patterns in molecular profiles and intra-patient genomic heterogeneity. In this Review, we highlight foundational and translational advances in dissecting the genomic cartography of GC, including non-coding variants, epigenomic aberrations and transcriptomic alterations, and describe how these alterations interplay with environmental influences, germline factors and the tumour microenvironment. Mapping of these alterations over the GC life cycle in normal gastric tissues, metaplasia, primary carcinoma and distant metastasis will improve our understanding of biological mechanisms driving GC development and promoting cancer hallmarks. On the translational front, integrative genomic approaches are identifying diverse mechanisms of GC therapy resistance and emerging preclinical targets, enabled by technologies such as single-cell sequencing and liquid biopsies. Validating these insights will require specifically designed GC cohorts, converging multi-modal genomic data with longitudinal data on therapeutic challenges and patient outcomes. Genomic findings from these studies will facilitate 'next-generation' clinical initiatives in GC precision oncology and prevention.
Insights
This review explores gastric cancer (GC) genomics, detailing alterations from early stages to metastasis. Understanding these genomic maps aids in developing targeted therapies and improving precision oncology for gastric cancer patients.
Area of Science:
- Genomic Medicine
- Cancer Genomics
- Translational Oncology
Background:
- Gastric cancer (GC) remains a significant global health challenge, with initial genomic studies identifying key driver alterations and molecular subtypes.
- Clinical application of these findings has been limited by complex genomic profiles and intra-patient heterogeneity.
Purpose of the Study:
- To review foundational and translational advances in gastric cancer genomics.
- To explore the interplay of genomic alterations with environmental, germline, and tumor microenvironment factors.
- To highlight how comprehensive genomic mapping aids in understanding GC development and therapy resistance.
Main Methods:
- Review of genomic studies, including non-coding variants, epigenomic, and transcriptomic alterations.
- Integration of multi-modal genomic data with clinical and longitudinal patient information.
- Application of advanced technologies like single-cell sequencing and liquid biopsies.
Main Results:
- Genomic cartography of GC reveals complex co-alteration patterns and intra-patient heterogeneity.
- Mapping alterations across the GC life cycle (normal tissue to metastasis) enhances understanding of cancer hallmarks.
- Integrative genomic approaches identify mechanisms of therapy resistance and potential preclinical targets.
Conclusions:
- Comprehensive genomic analysis across the GC lifecycle is crucial for understanding disease progression.
- Advanced genomic technologies and integrative approaches are vital for identifying novel therapeutic targets and overcoming resistance.
- Future clinical initiatives in GC precision oncology and prevention will be driven by these genomic insights.
