PIK3CA mutation and amplification in human lung cancer.
To explore the significance of phosphatidylinositol-3-kinase, catalytic, alpha (PIK3CA) in the carcinogenesis in human lung, mutations and copy number changes were investigated in 148 Japanese patients with primary cancer of the lung. For biological validation, the effects of exogenously expressed wild-type and mutated PIK3CA were studied in an immortalized human airway epithelial cell line. Mutations in PIK3CA were found in five (3.6%) of the 139 available patients, and copy number gains were found in 21 (18.3%) of 115 patients, respectively. Overall, mutations or copy number gains were detected in 24 of the 106 patients (22.6%) for whom results in both analyses were available. The prevalence of copy number gains was higher in men, smokers, and in patients with squamous cell carcinoma than in the opposite categories. The copy number changes showed a trend toward higher prevalence in the earlier stages (P = 0.038). Interestingly, the presence of mutations and of copy number alterations were mutually exclusive in the present patients, implying that both entail equivalent oncogenic potential. Over-expressed wild-type PIK3CA and its two common mutants, K545E and H1047R, significantly enhanced the anchorage-independent growth activity and migration activity of immortalized airway epithelium 16HBE14o- cells, but the effects of the K545E and H1047R mutants were more remarkable than those of the wild-type. The present demonstrates an important role of PIK3CA in human lung carcinogenesis.
Okudela
Koji
K
Department of Pathology I, Hamamatsu Universit School of Medicine, Hamamatsu, Japan.
Suzuki
Masaya
M
Kageyama
Shinji
S
Bunai
Tomoyasu
T
Nagura
Kiyoko
K
Igarashi
Hisaki
H
Takamochi
Kazuya
K
Suzuki
Kazuya
K
Yamada
Takeshi
T
Niwa
Hiroshi
H
Ohashi
Riuko
R
Ogawa
Hiroshi
H
Mori
Hiroki
H
Kitamura
Hitoshi
H
Kaneko
Takeshi
T
Tsuneyoshi
Toshihiro
T
Sugimura
Haruhiko
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018196:Carcinoma, Adenosquamous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002461:Cell Line, Transformed; D058534:Class I Phosphatidylinositol 3-Kinases; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism