Somatic mutations in epidermal growth factor receptor signaling pathway genes in non-small cell lung cancers

J Thorac Oncol. 2010 Nov;5(11):1734-40. doi: 10.1097/JTO.0b013e3181f0beca.

Abstract

Introduction: Epidermal growth factor receptor (EGFR) signaling pathway plays a crucial role in the development and progression of lung cancer. We searched for mutations of EGFR pathway genes in non-small cell lung cancers (NSCLCs) and analyzed their relationship with clinicopathologic features.

Methods: Mutations of EGFR, ERBB2, ERBB3, ERBB4, KRAS, NRAS, BRAF, PTEN, PIK3CA, LKB1, and AKT1 genes were determined by direct sequencing in 173 surgically resected NSCLCs--56 squamous cell carcinomas (SCCs) and 117 adenocarcinomas (ACs).

Results: Of the 173 NSCLCs, a total of 65 mutations were detected in 63 (36.4%) tumors--10 (17.9%) in SCCs and 53 (45.3%) in ACs. Mutations in EGFR pathway genes were significantly more frequent in women and ACs than in women and SCCs (p = 0.02 and p < 0.001, respectively). The mutations occurred in a mutually exclusive pattern. When the genes were divided into three subgroups according to their roles in the signaling cascade, mutations in the EGFR/ERBB2 and KRAS/BRAF genes were more frequent in ACs than in SCCs (p < 0.001 and p = 0.01, respectively). In marked contrast, mutations in the PIK3CA/PTEN were more frequent in SCCs than in ACs (p = 0.002). Furthermore, mutations in the PIK3CA/PTEN genes were more frequent in smokers (p = 0.04).

Discussion: Our study demonstrates that mutations in each part of the EGFR pathway were associated with different clinicopathologic features in patients with NSCLCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Class I Phosphatidylinositol 3-Kinases
  • ErbB Receptors / genetics*
  • Female
  • Genes, ras / genetics
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Neoplasm Staging
  • PTEN Phosphohydrolase / genetics
  • Phosphatidylinositol 3-Kinases / genetics
  • Prognosis
  • Protein-Serine-Threonine Kinases / genetics
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-3 / genetics
  • Receptor, ErbB-4
  • Signal Transduction / genetics*
  • ras Proteins / genetics

Substances

  • Biomarkers, Tumor
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Phosphatidylinositol 3-Kinases
  • STK11 protein, human
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • EGFR protein, human
  • ERBB2 protein, human
  • ERBB4 protein, human
  • ErbB Receptors
  • Receptor, ErbB-2
  • Receptor, ErbB-3
  • Receptor, ErbB-4
  • AKT1 protein, human
  • BRAF protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins