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High Frequency of Juxtamembrane Domain ERBB2 Mutation in Gastric Cancer

Sujin Park1, Soomin Ahn2, Deok Geun Kim3,4

  • 1Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Cancer Genomics & Proteomics
|December 24, 2021
PubMed
Abstract

Insights

ERBB2 mutations are found in gastric cancer but do not correlate with HER2 overexpression. The most common ERBB2 mutation, p.Arg678Gln, is located in the juxtamembrane domain.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • ERBB2 (Erb-B2 Receptor Tyrosine Kinase 2) mutations represent a novel therapeutic target in various solid tumors.
  • The specific mutation profiles and their association with human epidermal growth factor receptor 2 (HER2) overexpression in gastric cancer are not well-characterized.
  • Understanding these mutations is crucial for developing targeted therapies in gastric cancer.

Purpose of the Study:

  • To investigate the frequency, characteristics, and clinicopathological correlations of ERBB2 mutations in advanced gastric cancer.
  • To determine the relationship between ERBB2 mutations and HER2 expression in gastric cancer patients.
  • To identify common ERBB2 mutation hotspots in gastric cancer and compare them with public databases.

Main Methods:

  • Comprehensive panel sequencing was utilized to analyze tumor samples from 234 advanced gastric cancer patients.
  • Clinicopathological features of patients with ERBB2 mutations were documented.
  • ERBB2 mutation hotspots were analyzed in both the study cohort and a public database.

Main Results:

  • ERBB2 mutations were identified in 7.7% (18 out of 234) of advanced gastric cancer patients.
  • The most prevalent mutation was p.Arg678Gln (42.1% of mutations), located in the juxtamembrane domain of ERBB2.
  • None of the ERBB2-mutant patients exhibited HER2 overexpression; common co-occurring mutations included KRAS, PIK3CA, and ATM.

Conclusions:

  • ERBB2 mutations in gastric cancer are distinct from HER2 overexpression and do not appear to be associated.
  • The juxtamembrane domain is a frequent site for ERBB2 mutations in gastric cancer, with p.Arg678Gln being the most common.
  • These findings highlight the importance of molecular profiling for identifying actionable ERBB2 mutations in gastric cancer, independent of HER2 expression levels.
Keywords:
ERBB2 mutationHER2gastric cancertarget therapy

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