PTEN mutations and relationship to EGFR, ERBB2, KRAS, and TP53 mutations in non-small cell lung cancers

Lung Cancer. 2010 Sep;69(3):279-83. doi: 10.1016/j.lungcan.2009.11.012. Epub 2009 Dec 16.


Somatic mutations of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in non-small cell lung cancers (NSCLCs) have been investigated in but a small number of cases. In addition, the relationship between PTEN mutations and epidermal growth factor receptor (EGFR), KRAS, and TP53 mutations has not been investigated. Therefore, we investigated the frequency of PTEN mutations in 176 surgically resected NSCLCs and analyzed the relationship between PTEN mutations and EGFR, ERBB2, KRAS, and TP53 mutations. Mutations of PTEN (exons 1-9), EGFR (exons 18-21), ERBB2 (exons 19 and 20), KRAS (exon 1), and TP53 (exons 2-11) were determined by polymerase chain reaction and direct sequencing. PTEN mutations were present in 8 (4.5%) of the 176 tumors. PTEN mutations were only found in ever-smokers and were significantly more frequent in squamous cell carcinoma than in adenocarcinoma (10.2% vs 1.7%, P=0.02). Mutations of EGFR, ERBB2, KRAS, and TP53 genes were found in 36 (20.5%), 2 (1.1%), 11 (6.3%), and 66 (37.5%) cases, respectively. Of the 8 tumors with PTEN mutations, 1 case concurrently had an EGFR mutation and 4 cases had TP53 mutations. However, PTEN mutations were not found in the tumors with KRAS mutation. Our findings indicate that PTEN mutations are relatively common in NSCLC, and thus analysis of PTEN mutations may facilitate a comprehensive understanding of the genetic alterations related to the EGFR signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / surgery
  • DNA Mutational Analysis
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Mutation / genetics*
  • PTEN Phosphohydrolase / genetics*
  • PTEN Phosphohydrolase / metabolism
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Receptor, ErbB-2 / genetics
  • Signal Transduction / genetics
  • Tumor Suppressor Protein p53 / genetics
  • ras Proteins / genetics


  • KRAS protein, human
  • Proto-Oncogene Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • EGFR protein, human
  • ERBB2 protein, human
  • ErbB Receptors
  • Receptor, ErbB-2
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins