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Somatic mutations of ERBB2 kinase domain in gastric, colorectal, and breast carcinomas

Jong Woo Lee1, Young Hwa Soung, Si Hyung Seo

  • 1Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|January 7, 2006
PubMed
Abstract

Insights

ERBB2 kinase domain mutations are found in gastric, breast, and colorectal cancers, not just lung cancer. These ERBB2 mutations, sometimes with K-RAS mutations, may drive cancer development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The ERBB2 gene's kinase domain is somatically mutated in lung adenocarcinoma, indicating its oncogenic potential.
  • Previous research on ERBB2 mutations has predominantly focused on lung cancers, leaving data on other cancer types largely unknown.

Purpose of the Study:

  • To investigate the frequency and spectrum of ERBB2 kinase domain mutations in gastric, colorectal, and breast carcinomas.
  • To explore the co-occurrence of ERBB2 mutations with other cancer-associated gene mutations (EGFR, K-RAS, PIK3CA, BRAF).

Main Methods:

  • PCR single-strand conformational polymorphism (SSCP) assay was employed for mutational analysis.
  • Analysis was performed on DNA extracted from gastric, colorectal, and breast carcinoma tissues.
  • Somatic mutations in EGFR, K-RAS, PIK3CA, and BRAF were analyzed in samples with ERBB2 mutations.

Main Results:

  • ERBB2 kinase domain mutations were detected in 5.0% of gastric (9/180), 2.9% of colorectal (3/104), and 4.3% of breast (4/94) carcinomas.
  • Most ERBB2 mutations were missense, with specific mutations affecting Val777 (exon 20) and Leu755 (exon 19).
  • All three colorectal cancer samples with ERBB2 mutations also harbored K-RAS mutations.

Conclusions:

  • ERBB2 kinase domain mutations occur in common human cancers beyond lung adenocarcinoma, including gastric, breast, and colorectal cancers.
  • Alterations in the ERBB2-mediated signaling pathway, driven by ERBB2 mutations alone or in conjunction with K-RAS mutations, may contribute to human cancer development.

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