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ATM – Gastric Carcinoma

Somatic alterations of ATM have been identified in gastric carcinoma. In a cohort of microsatellite instability–positive tumors, frameshift mutations in ATM were detected in 3 of 36 cases (PMID:11196187), and immunohistochemistry in 249 gastric carcinoma samples revealed low ATM protein expression in 80 cases (PMID:39476606). Low ATM expression correlated with older age, specific histologic subtypes, lower disease stage, and MSI-high status, and somatic ATM mutations co-occurred significantly with ARID1A mutations in independent SMC (N = 813) and TCGA-STAD (N = 431) cohorts (PMID:39476606).

Functional evidence in gastric carcinoma indicates that ATM loss-of-function is associated with increased tumor-infiltrating lymphocytes and a favorable prognosis, suggesting a tumor suppressor role for ATM in gastric epithelium. Despite these correlations, mechanistic studies directly modeling ATM deficiency in gastric cancer remain limited, representing an opportunity for therapeutic development.

Key Take-home: Somatic ATM loss in gastric carcinoma is a rare but recurrent feature in MSI-positive tumors, with potential utility as a prognostic biomarker and therapeutic target.

References

  • Pathology, research and practice • 2024 • Association of ATM and ARID1A in gastric carcinoma. PMID:39476606
  • Cancer research • 2001 • Frameshift mutations at coding mononucleotide repeats of the hRAD50 gene in gastrointestinal carcinomas with microsatellite instability. PMID:11196187

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Somatic ATM frameshift mutations in 3 MSI-positive gastric carcinoma cases and low ATM expression in 80 of 249 gastric carcinoma samples with clinicopathological correlation ([PMID:11196187], [PMID:39476606])

Genetic Evidence

Limited

Somatic ATM frameshift mutations identified in 3 of 36 MSI-positive gastric carcinoma cases ([PMID:11196187]) and ATMlow in 80 of 249 IHC‐stained gastric carcinoma samples ([PMID:39476606])

Functional Evidence

Limited

ATMlow in gastric carcinoma correlates with increased tumor-infiltrating lymphocytes and favorable prognosis, indicating loss-of-function in disease context ([PMID:39476606])