PIK3CA mutation is an oncogenic aberration at advanced stages of oral squamous cell carcinoma

Ken Ichi Kozaki, Issei Imoto, Atiphan Pimkhaokham, Shogo Hasegawa, Hitoshi Tsuda, Ken Omura, Johji Inazawa

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Phosphatidylinositol 3-kinases (PI3K) are a group of heterodimeric lipid kinases that regulate many cellular processes. Gene amplification and somatic mutations mainly within the helical (exon 9) and kinase (exon 20) domains of PIK3CA, which encode the 110-kDa catalytic subunit of PI3K and are mapped to 3q26, have been reported in various human cancers. Herein, 14 human oral squamous cell carcinoma (OSCC) cell lines and 108 primary OSCC tumors were investigated for activating mutations at exons 9 and 20 as well as amplifications in PIK3CA. PIK3CA missense mutations in exons 9 and 20 were identified in 21.4% (3/14) of OSCC cell lines and 7.4% (8/108) of OSCC tumors by genomic DNA sequencing. An increase in the copy number of PIK3CA, although small, was detected in 57.1% (8/14) of OSCC lines and 16.7% (18/108) of OSCC tumors using quantitative real-time PCR. A significant correlation between somatic mutations of PIK3CA and disease stage was observed: the frequency of mutations was higher in stage IV (16.1%, 5/31) than in a subset of early stages (stages I-III) (3.9%, 3/77; P = 0.042, Fisher's extract test). In contrast, the amplification of PIK3CA was observed at a similar frequency among all stages. AKT was highly phosphorylated in OSCC cell lines with PIK3CA mutations compared to those without mutations, despite the amplification. The results suggest that somatic mutations of the PIK3CA gene are likely to occur late in the development of OSCC, and play a crucial role through the PI3K-AKT signaling pathway in cancer progression.

Original languageEnglish
Pages (from-to)1351-1358
Number of pages8
JournalCancer Science
Volume97
Issue number12
DOIs
Publication statusPublished - Dec 2006
Externally publishedYes

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Oral Stage
Squamous Cell Carcinoma
Mutation
Exons
Phosphatidylinositol 3-Kinases
Cell Line
Neoplasms
Phosphotransferases
Gene Amplification
Mutation Rate
Missense Mutation
DNA Sequence Analysis
Real-Time Polymerase Chain Reaction
Catalytic Domain
Lipids

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kozaki, K. I., Imoto, I., Pimkhaokham, A., Hasegawa, S., Tsuda, H., Omura, K., & Inazawa, J. (2006). PIK3CA mutation is an oncogenic aberration at advanced stages of oral squamous cell carcinoma. Cancer Science, 97(12), 1351-1358. https://doi.org/10.1111/j.1349-7006.2006.00343.x

PIK3CA mutation is an oncogenic aberration at advanced stages of oral squamous cell carcinoma. / Kozaki, Ken Ichi; Imoto, Issei; Pimkhaokham, Atiphan; Hasegawa, Shogo; Tsuda, Hitoshi; Omura, Ken; Inazawa, Johji.

In: Cancer Science, Vol. 97, No. 12, 12.2006, p. 1351-1358.

Research output: Contribution to journalArticle

Kozaki, KI, Imoto, I, Pimkhaokham, A, Hasegawa, S, Tsuda, H, Omura, K & Inazawa, J 2006, 'PIK3CA mutation is an oncogenic aberration at advanced stages of oral squamous cell carcinoma', Cancer Science, vol. 97, no. 12, pp. 1351-1358. https://doi.org/10.1111/j.1349-7006.2006.00343.x
Kozaki, Ken Ichi ; Imoto, Issei ; Pimkhaokham, Atiphan ; Hasegawa, Shogo ; Tsuda, Hitoshi ; Omura, Ken ; Inazawa, Johji. / PIK3CA mutation is an oncogenic aberration at advanced stages of oral squamous cell carcinoma. In: Cancer Science. 2006 ; Vol. 97, No. 12. pp. 1351-1358.
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abstract = "Phosphatidylinositol 3-kinases (PI3K) are a group of heterodimeric lipid kinases that regulate many cellular processes. Gene amplification and somatic mutations mainly within the helical (exon 9) and kinase (exon 20) domains of PIK3CA, which encode the 110-kDa catalytic subunit of PI3K and are mapped to 3q26, have been reported in various human cancers. Herein, 14 human oral squamous cell carcinoma (OSCC) cell lines and 108 primary OSCC tumors were investigated for activating mutations at exons 9 and 20 as well as amplifications in PIK3CA. PIK3CA missense mutations in exons 9 and 20 were identified in 21.4{\%} (3/14) of OSCC cell lines and 7.4{\%} (8/108) of OSCC tumors by genomic DNA sequencing. An increase in the copy number of PIK3CA, although small, was detected in 57.1{\%} (8/14) of OSCC lines and 16.7{\%} (18/108) of OSCC tumors using quantitative real-time PCR. A significant correlation between somatic mutations of PIK3CA and disease stage was observed: the frequency of mutations was higher in stage IV (16.1{\%}, 5/31) than in a subset of early stages (stages I-III) (3.9{\%}, 3/77; P = 0.042, Fisher's extract test). In contrast, the amplification of PIK3CA was observed at a similar frequency among all stages. AKT was highly phosphorylated in OSCC cell lines with PIK3CA mutations compared to those without mutations, despite the amplification. The results suggest that somatic mutations of the PIK3CA gene are likely to occur late in the development of OSCC, and play a crucial role through the PI3K-AKT signaling pathway in cancer progression.",
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