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Coamplified and overexpressed genes at ERBB2 locus in gastric cancer

Asta Varis1, Alexander Zaika, Pauli Puolakkainen

  • 1Departments of Pathology and Medical Genetics, Haartman Institute, University of Helsinki and Helsinki University Central Hospital Laboratory Diagnostics, Helsinki, Finland.

International Journal of Cancer
|March 3, 2004
PubMed

Insights

Amplification of 17q21 genes, including ERBB2, TOP2A, and DARPP32, occurs in gastric cancer. DARPP32 showed frequent overexpression at both RNA and protein levels, suggesting its potential role.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Gastric cancer frequently exhibits DNA copy number amplification at the 17q chromosomal region.
  • The 17q21 region is critical for amplicon formation, containing oncogenes like ERBB2 and other targets such as TOP2A and DARPP32.

Purpose of the Study:

  • To characterize the amplification and expression levels of ERBB2, TOP2A, and DARPP32 in gastric cancer samples.
  • To investigate the correlation between gene amplification and gene expression of these targets.

Main Methods:

  • Analysis of gene amplification in 52 gastric cancer samples.
  • Quantitative real-time PCR to assess gene expression in 29 gastric cancer samples.
  • Immunohistochemistry to evaluate protein overexpression in 66 gastric cancer samples.

Main Results:

  • Concomitant amplification of ERBB2, TOP2A, and DARPP32 was observed in 17% of intestinal type gastric adenocarcinomas.
  • Gene expression levels were independent of amplification, with DARPP32 showing the highest overexpression (48%), followed by TOP2A (17%) and ERBB2 (3%).
  • DARPP32 protein overexpression was detected in 45% of gastric cancer cases.

Conclusions:

  • DARPP32 is the most frequently overexpressed gene among the studied targets in gastric cancer.
  • While co-amplification occurs, gene expression appears independent, highlighting DARPP32's significant protein overexpression.
  • Further research is needed to elucidate the biological significance of these genes in gastric cancer development and progression.

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