Cells with TP53 mutations in low grade astrocytic tumors evolve clonally to malignancy and are an unfavorable prognostic factor

Details

Serval ID
serval:BIB_B057360C2496
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cells with TP53 mutations in low grade astrocytic tumors evolve clonally to malignancy and are an unfavorable prognostic factor
Journal
Oncogene
Author(s)
Ishii  N., Tada  M., Hamou  M. F., Janzer  R. C., Meagher-Villemure  K., Wiestler  O. D., Tribolet  N., Van Meir  E. G.
ISSN
0950-9232 (Print)
Publication state
Published
Issued date
1999
Volume
18
Number
43
Pages
5870-5878
Notes
PT - Journal Article PT - Research Support, Non-U.S. Gov't
Abstract
It is important to understand how low grade tumors recur and progress to malignant lesions since this dramatically shortens patient survival. Here, we evaluated the concept that malignant progression and poor prognosis of low grade astrocytic tumors are TP53 dependent through clonal expansion of mutated cells. TP53 status was established in primary and recurrent tumors from 36 patients with WHO grade II astrocytic tumors and two tumor types were found. Tumors from 14 patients (39%; type 1) had TP53 mutated cells, and 92% of these recurred with 57% progressing to malignancy. The evolution of TP53 mutated cells before and after progression was examined using a clonal analysis procedure in yeast. Malignant progression was accompanied by an increased percentage of mutant TP53 (red) yeast colonies resulting from monoclonal expansion of cells with mutated TP53. The presence of TP53 mutations in WHO grade II astrocytic tumors was associated with malignant progression (P=0. 034, chi2 test) and shorter progression-free survival (PFS; 47.6+/-9. 6 months for TP53-mutated tumors vs 67.8+/-8.2 months for TP53-wild type tumors, P<0.05, log-rank test). Tumors from 22 patients (61%; type 2) were without TP53 mutations, and 64% of these recurred without a change in TP53 status, although 41% progressed to malignancy. This suggests that TP53 mutation is not an initiating or progression event in the majority of low grade astrocytic tumors. Our study also indicates that irradiation for WHO grade II astrocytic tumors might be associated with poor outcome (P<0.0001) and this was independent of TP53 status. These findings have important implications in the clinical management of patients with low grade astocytoma and provide new support to the clonal evolution model for tumor progression
Keywords
Adolescent/Adult/Aged/Astrocytoma/classification/genetics/physiopathology/radiotherapy/Brain Neoplasms/Child,Preschool/Clone Cells/Disease Progression/Female/Humans/Male/Middle Aged/Mutation/Prognosis/Recurrence/Tumor Suppressor Protein p53
Pubmed
Web of science
Open Access
Yes
Create date
29/01/2008 18:34
Last modification date
20/08/2019 15:19
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