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Somatic mutations of the ERBB4 kinase domain in human cancers

Young Hwa Soung1, Jong Woo Lee, Su Young Kim

  • 1Department of Pathology, College of Medicine, Catholic University of Korea, Seoul 137-701, Korea.

International Journal of Cancer
|September 28, 2005
PubMed

Insights

Somatic mutations in the ERBB4 kinase domain are found in common human cancers like stomach, lung, colon, and breast. These ERBB4 mutations may contribute to cancer development by altering signaling pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The Epidermal Growth Factor Receptor (EGFR) family includes four receptor tyrosine kinases: EGFR (ERBB1), ERBB2 (HER2), ERBB3 (HER3), and ERBB4 (HER4).
  • Previous research identified somatic mutations in the kinase domains of EGFR (ERBB1) and ERBB2 (HER2) in human cancers.
  • This suggests that other ERBB family members, including ERBB4, might also harbor somatic mutations in various cancers.

Purpose of the Study:

  • To investigate the presence and frequency of somatic mutations within the ERBB4 kinase domain across multiple common human cancer types.
  • To characterize the types of ERBB4 mutations detected.
  • To explore potential co-mutations with other cancer-associated genes in samples harboring ERBB4 mutations.

Main Methods:

  • Mutational analysis of the ERBB4 kinase domain was performed using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) assay.
  • The study analyzed 595 cancer tissue samples from stomach, lung, colon, and breast.
  • Simultaneous analysis of somatic mutations in EGFR, ERBB2, K-RAS, PIK3CA, and BRAF genes was conducted on samples with ERBB4 mutations.

Main Results:

  • ERBB4 somatic mutations were detected in gastric (1.7%), colorectal (2.9%), non-small cell lung (2.3%), and breast (1.1%) carcinomas.
  • A total of 12 ERBB4 mutations were identified, including 1 in-frame duplication, 8 missense mutations in exons, and 3 intronic mutations.
  • One gastric carcinoma with an ERBB4 mutation also showed a co-existing K-RAS gene mutation.

Conclusions:

  • Somatic mutations in the kinase domain of ERBB4 occur in common human cancers, similar to EGFR and ERBB2.
  • These ERBB4 mutations may play a role in tumorigenesis.
  • Alterations in the ERBB4-mediated signaling pathway due to ERBB4 mutations could contribute to human cancer development.

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