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Updated: Jul 5, 2026

Detection of a CDH1 Rare Transcript Variant in Fresh-frozen Gastric Cancer Tissues by Chip-based Digital PCR
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Detection of a CDH1 Rare Transcript Variant in Fresh-frozen Gastric Cancer Tissues by Chip-based Digital PCR

Published on: February 5, 2018

The NMD mRNA surveillance pathway downregulates aberrant E-cadherin transcripts in gastric cancer cells and in CDH1

R Karam1, J Carvalho, I Bruno

  • 1Cancer Genetics Group, Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Porto, Portugal.

Oncogene
|April 23, 2008
PubMed

Insights

Nonsense-mediated decay (NMD) downregulates tumor suppressor E-cadherin (CDH1) transcripts with premature termination codons (PTCs) in hereditary diffuse gastric cancer (HDGC). This NMD activity may worsen patient outcomes, suggesting NMD as a therapeutic target.

Area of Science:

  • Genetics
  • Molecular Biology
  • Cancer Research

Background:

  • Germline mutations in the E-cadherin (CDH1) gene cause hereditary diffuse gastric cancer (HDGC).
  • Approximately 80% of CDH1 mutations in HDGC patients lead to premature termination codons (PTCs).

Purpose of the Study:

  • To investigate if nonsense-mediated decay (NMD) downregulates CDH1 transcripts containing PTCs.
  • To explore the role of NMD in HDGC pathogenesis and its potential as a therapeutic target.

Main Methods:

  • Utilized an allele-specific expression (ASE) assay to distinguish between mutated and wild-type CDH1 alleles.
  • Examined CDH1 transcript levels in normal gastric tissue from HDGC carriers and in the KATO-III gastric tumor cell line.
  • Assessed the effect of protein synthesis inhibitors and depletion of NMD factors (UPF1, eIF4AIII) on CDH1 transcript levels.

Main Results:

  • PTC-bearing CDH1 mRNAs were significantly downregulated in normal gastric tissue from HDGC mutation carriers.
  • NMD was confirmed as the mechanism responsible for CDH1 transcript downregulation.
  • CDH1 transcripts with PTCs were upregulated upon NMD inhibition in a gastric tumor cell line.
  • A correlation was found between the predicted NMD-inducing ability of CDH1 PTCs and an earlier age of gastric cancer onset in HDGC patients.

Conclusions:

  • Nonsense-mediated decay (NMD) actively degrades CDH1 transcripts with premature termination codons (PTCs).
  • NMD's role in downregulating CDH1 may contribute to earlier onset of gastric cancer in HDGC patients.
  • NMD represents a potential therapeutic target for individuals with CDH1 mutations and HDGC.

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