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Related Experiment Videos

Differences in genomic instability between intestinal- and diffuse-type gastric cancer.

Matti Vauhkonen1, Hanna Vauhkonen, Antti Sajantila

  • 1Department of Medicine, HUCH, Jorvi Hospital, Turuntie 150, 02740 Espoo, Finland.

Gastric Cancer : Official Journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
|December 6, 2005
PubMed
Summary

Gastric carcinoma subtypes show distinct genomic instability. Intestinal-type GCA frequently exhibits microsatellite instability (MSI) and loss of heterozygosity (LOH), while diffuse-type GCA predominantly displays a stable phenotype.

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Area of Science:

  • Genomics
  • Cancer Biology
  • Molecular Pathology

Background:

  • Microsatellite instability (MSI) and loss of heterozygosity (LOH) are common genomic alterations in gastric carcinomas (GCAs).
  • Previous studies have not systematically classified MSI and LOH in the two main GCA subtypes: intestinal-type (IGCA) and diffuse-type (DGCA).

Purpose of the Study:

  • To systematically classify MSI and LOH in IGCA and DGCA.
  • To investigate the distinct patterns of genomic instability in these GCA subtypes.

Main Methods:

  • Assayed 37 advanced GCAs (25 IGCA, 12 DGCA) using 15 autosomal tetranucleotide markers.
  • Stratified tumors into high- and low-grade MSI (MSI-H, MSI-L) or microsatellite-stable (MSS) phenotypes.
  • Stratified tumors into high- or low-grade, or non-detectable LOH (LOH-H, LOH-L, LOH-N) phenotypes.

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Main Results:

  • MSI-H and LOH-H were significantly associated with IGCA (92% of cases), with 7 MSI-H and 6 LOH-H tumors identified.
  • DGCA showed a significantly higher prevalence of a stable (LOH-N/MSS) phenotype (75.1%) compared to IGCA (28.0%).
  • The MSI-L phenotype was observed in 57.9% of non-MSI-H IGCA tumors and was significantly associated with LOH-H.

Conclusions:

  • Significant differences in genomic instability exist between IGCA and DGCA.
  • IGCA is characterized by increased involvement of MSI and LOH pathways.
  • DGCA predominantly exhibits a stable phenotype, with MSI-L and LOH association identified as a novel finding in IGCA.