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Updated: Aug 7, 2026
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Primary Tumor Genomics and Patterns of Distant Recurrence in Resected Gastric Cancer
Max R Coffey1, Jierui Xu2, Pranita Atri2
1Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
Importance:
Patients with gastric cancer face substantial risk of recurrence after surgical resection. Molecular profiling of primary tumors may improve risk stratification to guide postoperative management.
Objective:
To identify genomic features of primary gastric tumors associated with disease recurrence and patterns of metastatic spread.
Design, Setting, And Participants:
This single-center cohort study took place at an academic quaternary referral center and included patients who underwent curative-intent resection of gastric adenocarcinoma from 2010 to 2024. Patients were classified by recurrence status and pattern of metastatic spread. Patients with gastric cancer (stages I to III) who underwent a margin-negative resection and had genomic sequencing of their primary tumor were included. Primary analysis excluded patients who had no evidence of disease with less than 2 years of follow-up. These data were analyzed from June 2025 through March 2026.
Exposures:
Primary tumor specimens were sequenced using a targeted panel of cancer-associated genes (MSK-IMPACT).
Main Outcomes And Measures:
Correlation of disease-free survival and patterns of metastatic spread (hematogenous, peritoneal, or lymphatic) with primary tumor genomic profile.
Results:
Among 438 patients who underwent complete oncologic resection, 377 had sufficient clinical follow-up or developed recurrence (median [IQR] age, 64 [55-71] years; 113 female [30%] and 264 male [70%]). Recurrence was identified in 179 patients, whereas 198 patients had no evidence of disease. In a multivariable analysis, alterations in KRAS (hazard ratio [HR], 1.54; 95% CI, 1.04-2.28; P = .03) and PIK3CA (HR, 2.15; 95% CI, 1.25-3.69; P = .006) were independently associated with worse disease-free survival. Tumors of patients with hematogenous recurrence had greater chromosomal instability (fraction genome altered, 0.11 vs 0.03; P = .001), whole-genome duplication (47% vs 15%; P = .02), and more frequent alterations of genes modulating cell cycle regulation (39% vs 6%; P < .001) compared with peritoneal recurrence. Bone metastasis arose from more genomically stable primary tumors (fraction genome altered, 0.005 vs 0.114; P < .001) and tumors with Lauren diffuse-type histology (36% vs 3%; P < .001) compared with other sites of hematogenous spread.
Conclusions And Relevance:
This study identifies genomic alterations associated with disease-free survival and patterns of recurrence after resection of gastric cancer. These clinicogenomic risk factors may personalize postoperative surveillance strategies and inform perioperative treatment decisions.
