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Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
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Somatic mutations of epidermal growth factor receptor in colorectal carcinoma

Hisashi Nagahara1, Koshi Mimori, Mitsuhiko Ohta

  • 1Department of Surgery, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu 874-0838, Japan.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|March 5, 2005
PubMed
Abstract

Insights

Somatic mutations in the epidermal growth factor receptor (EGFR) gene were found in 12% of colorectal adenocarcinomas. These EGFR mutations suggest potential sensitivity to gefitinib treatment in a subset of patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Somatic mutations in the epidermal growth factor receptor (EGFR) gene are established biomarkers for gefitinib sensitivity in non-small cell lung carcinoma.
  • EGFR mutations have not been previously reported in colorectal carcinoma.

Purpose of the Study:

  • To investigate the presence and frequency of somatic mutations in the EGFR gene within colorectal adenocarcinomas.
  • To explore the potential implications of EGFR mutations for targeted therapy with gefitinib in colorectal cancer.

Main Methods:

  • Analysis of 11 colorectal adenocarcinoma cell lines and 33 clinical colorectal carcinoma samples.
  • Utilized laser microdissection to isolate carcinoma cells from frozen tissue sections.
  • Performed DNA extraction, PCR amplification, and sequencing of the EGFR gene to identify mutations.

Main Results:

  • No somatic EGFR mutations were detected in any of the 11 colorectal carcinoma cell lines.
  • Somatic mutations within the EGFR kinase domain were identified in 4 out of 33 (12%) clinical colorectal tumors.
  • This represents a potential first report of somatic EGFR mutations in colorectal adenocarcinoma.

Conclusions:

  • A small proportion of colorectal adenocarcinomas harbor somatic mutations in the EGFR gene.
  • These EGFR-mutated colorectal tumors may represent a distinct subset susceptible to treatment with gefitinib.

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