title: 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.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Kyungpook National University, Dong In 2Ga 101, Daegu 700-422, Republic of Korea.
authors.forename: Guang
authors.initials: G
authors.lastname: Jin
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Kim
authors.forename: Hyo-Sung
authors.initials: HS
authors.lastname: Jeon
authors.forename: Jin Eun
authors.initials: JE
authors.lastname: Choi
authors.forename: Dong Sun
authors.initials: DS
authors.lastname: Kim
authors.forename: Eung Bae
authors.initials: EB
authors.lastname: Lee
authors.forename: Sung Ick
authors.initials: SI
authors.lastname: Cha
authors.forename: Ghil Sook
authors.initials: GS
authors.lastname: Yoon
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Kim
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Jung
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
chemical_list: D066246:ErbB Receptors; D051059:PTEN Phosphohydrolase; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; D018631:ras Proteins; C117307:KRAS protein, human; C495901:TP53 protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C494929:PTEN protein, human