Frequent Co‐Alterations of TP53, p16/CDKN2A, p14ARF, PTEN Tumor Suppressor Genes in Human Glioma Cell Lines.
In this study we established the simultaneous status of TP53, p16, p14
ARF and PTEN tumor suppressor genes in 34 randomly chosen human glioma cell lines. Nine cell lines (26.4%) harbored mutations or deletions in all four tumor suppressor genes and 22 cell lines
(64%) had alterations in at least three. Mutations/deletions were found at the following frequencies: TP53 (76.5%), p14
ARF (64.7%), p16 (64,7%), PTEN (73.5%). Thus, there was a high incidence of alterations in the cellular pathways involving the p53 transcription
factor (94.1%), the retinoblastoma protein (64.7%) and the PTEN phosphatase (73.5%) and 91% of cell lines carried mutations in two or more pathways. This provides the first clear genetic evidence that these tumor suppressors participate in biological pathways which are functioning separately/independently
in glioma cells. The status of the gene alterations did not correlate with tumorigenicity in immunocompromized mice or any clinical parameters. Although the mutation rate was higher in glioma cell lines than that reported for glioma tissues, the alterations were molecularly representative
of those found in adult de novo glioblastoma. This study highlights the importance of developing therapeutic approaches applicable to tumors with a broad range of genetic alterations and also provides an invaluable panel of glioma cell lines to make this possible.
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Document Type: Research Article
Laboratory of Tumor Biology and Genetics, Department of Neurosurgery, Centre Hospitalier Universitaire Vaudois (CHUV), rue du Bugnon 5, CH-1011, Lausanne, Switzerland
Molecular Neuro-Oncology, Neurosurgery and Department of Research, University Hospital, Schanzenstr. 46, CH-4031 Basel, Switzerland
Department of Neurosurgery, University of Hokkaido School of Medicine, Sapporo 060, Japan
July 1, 1999