Association of TP53 mutation, p53 overexpression, and p53 codon 72 polymorphism with susceptibility to apoptosis in adult patients with diffuse astrocytomas
| Autor: | N. Huang, S. K. Nagahashi-Marie, Sueli Mieko Oba-Shinjo, Alda Wakamatsu, Milberto Scaff, R. Marino Junior, Miyuki Uno, Paulo Henrique Pires de Aguiar, Sérgio Rosemberg, Flávio Kei Miura, Claudia da Costa Leite, V. Avancini Ferreira Alves |
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| Rok vydání: | 2006 |
| Předmět: |
0301 basic medicine
Adult Male Cancer Research Programmed cell death Clinical Biochemistry Caspase 3 Apoptosis Astrocytoma Pathology and Forensic Medicine 03 medical and health sciences 0302 clinical medicine Diffuse Astrocytoma Glioma Genotype medicine Biomarkers Tumor Humans neoplasms Caspase Aged Polymorphism Genetic biology Single-strand conformation polymorphism Middle Aged medicine.disease Genes p53 Molecular biology 030104 developmental biology Oncology 030220 oncology & carcinogenesis Caspases Mutation Cancer research biology.protein Tumor Suppressor Protein p53 |
| Zdroj: | ResearcherID |
| ISSN: | 0393-6155 |
| Popis: | Clarification of TP53 alterations is important to understand the mechanisms underlying the development of diffuse astrocytomas. It has been suggested that the alleles of TP53 at codon 72 differ in their ability to induce apoptosis in human cancers. The aim of this study was to analyze the possible association of TP53 mutation, p53 overexpression, and p53 codon 72 polymorphism with susceptibility to apoptosis in adult Brazilian patients with diffuse astrocytomas. We analyzed 56 surgical specimens of diffuse astrocytomas for alterations of TP53, using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) direct sequencing. p53 and cleaved caspase 3 protein expression were assessed by immunohistochemistry. We found TP53 mutations in 19.6% (11 out of 56) of tumors tested, with the lowest mutation rate found in the cases of glioblastomas (8.8%) (p = 0.03). Only 16.1% of tumors tested showed cleaved caspase 3-positive staining, demonstrating that apoptosis is very inhibited in these tumors. All tumors having TP53 mutation and p53 accumulation had no expression of cleaved caspase 3. Additionally, no association was observed in tumors having proline and arginine alleles and expression of cleaved caspase 3. We concluded that clarification of the TP53 alterations allows a better understanding of the mechanisms involved in the progression of diffuse astrocytomas, and the allele status at codon 72 was not associated with apoptosis in these tumors. |
| Databáze: | OpenAIRE |
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