Functional evaluation of p53 and PTEN gene mutations in gliomas

H. Kato, Shunsuke Kato, T. Kumabe, Yukihiko Sonoda, T. Yoshimoto, S. Kato, S. Han, T. Suzuki, H. Shibata, R. Kanamaru, C. Ishioka

Research output: Contribution to journalArticlepeer-review

80 Citations (Scopus)

Abstract

We screened mutations of two major tumor suppressor genes, p53 and PTEN, in 66 human brain tumors using a yeast-based functional assay and cDNA-based direct sequencing, respectively. The frequency of p53 mutations was 28.8% (19 of 66) and was higher in anaplastic astrocytoma (9 of 14, 64.3%,) than in glioblastoma multiforme (GBM; 7 of 27, 25.9%,), supporting previous speculation that there are at least two genetic pathways leading to GBM, a de novo pathway without p53 mutation and a 'progressive' pathway with p53 mutation. PTEN mutation was observed in 8 of 64. tumors (12.5%), mainly GBMs (7 of 26, 26.9%), both with and without p53 mutation. These results suggest that mutation of the PTEN gene is a later event than that of the p53 gene in glioma progression and is associated with both the genetic pathways. All of the detected PTEN missense mutations and an in-frame small deletion inactivated PTEN phosphoinositide phosphatase activity in vitro. Because the tumors containing PTEN mutations also showed loss of heterozygosity in the chromosome 10q23 region flanking the PTEN gene, our data clearly indicate that inactivation of both PTEN alleles occurs in a subset of high-grade gliomas, therefore confirming the previous idea that PTEN acts as a tumor suppressor gene.

Original languageEnglish
Pages (from-to)3937-3943
Number of pages7
JournalClinical Cancer Research
Volume6
Issue number10
Publication statusPublished - 2000 Nov 13

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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