ASSOCIATION OF P53 GENE MUTATION WITH DECREASED CHEMOSENSITIVITY IN HUMAN-MALIGNANT GLIOMAS

Loss of p53 function is involved in tumorigenesis of various human can cers, but the relation between mutation of the p53 tumor-suppressor ge ne and the chemo- and radiosensitivity of tumors remains unclear. Muta ted p53 gene in malignant glioma is often associated with progression and recurrence of malignancy, and these events are closely linked with increased resistance to both chemotherapy and radiation. We have exam ined the status of the p53 gene in malignant gliomas obtained from 34 patients (glioblastoma: 29 cases, anaplastic astrocytomas: 5 cases). T he chemosensitivities of these specimens using 28 kinds of anti-cancer agents were determined using an in vitro assay system. Overall, 12 mu tated cases of p53 gene were found in malignant glioma samples. The me an numbers of effective agents were 0.58 for the tumor samples with p5 3 mutations and 5.00 for tumors without mutations. Our data indicate t hat p53 gene mutation predisposes to decreased cell killing via chemot herapy in malignant gliomas. (C) 1996 Wiley-Liss, Inc.