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

Abstract

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.

• Authors: Guang Jin, Min Jung Kim, Hyo-Sung Jeon, Jin Eun Choi, Dong Sun Kim, Eung Bae Lee, Sung Ick Cha, Ghil Sook Yoon, Chang Ho Kim, Tae Hoon Jung, Jae Yong Park
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 69 Issue 3 Pg. 279-83 (Sep 2010) ISSN: 1872-8332 [Electronic] Ireland
• PMID: 20018398 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• 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

Topics

• Aged
• Carcinoma, Non-Small-Cell Lung (genetics, metabolism, pathology, surgery)
• DNA Mutational Analysis
• ErbB Receptors (genetics, metabolism)
• Female
• Humans
• Lung Neoplasms (genetics, metabolism, pathology, surgery)
• Male
• Middle Aged
• Mutation (genetics)
• PTEN Phosphohydrolase (genetics, 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)