TP53 mutations in astrocytic gliomas: an association with histological grade, TP53 codon 72 polymorphism and p53 expression

• Published in: APMIS : acta pathologica, microbiologica et immunologica Scandinavica microbiologica et immunologica Scandinavica, 2012-11, Vol.120 (11), p.882-889
• Main Authors: Faria, Mario H. G., Neves Filho, Eduardo H. C., Alves, Markenia K. S., Burbano, Rommel M. R., de Moraes Filho, Manoel O., Rabenhorst, Silvia H. B.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; astrocytic tumors; Astrocytoma - genetics; Astrocytoma - metabolism; Astrocytoma - pathology; Biological and medical sciences; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Cell cycle; Child; Child, Preschool; Codon; DNA repair; DNA sequencing; DNA, Neoplasm - genetics; Exons; Female; Fundamental and applied biological sciences. Psychology; Genes, p53; Humans; Infectious diseases; Male; Medical research; Medical sciences; Microbiology; Middle Aged; Mutation; p53 expression; Polymorphism, Genetic; Sequence Analysis, DNA; TP53 mutation; TP53 polymorphism; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumors; Young Adult
• ISSN: 0903-4641; 1600-0463
• DOI: 10.1111/j.1600-0463.2012.02918.x

TP53 mutations and polymorphisms have been widely related to many cancers as long as these alterations may impair its capacity to induce cell cycle arrest, DNA repair mechanisms, and apoptosis. Although TP53 alterations have been studied in astrocytic tumors, there is a lack of analysis considering specific TP53 mutations and their associations with p53 immunostainning, polymorphisms and their significance among the histological grades. Thus, we analyzed TP53 alterations in exons 2–11, including the codon 72 polymorphism, using DNA sequencing in 96 astrocytic gliomas (18 grade I, 20 grade II, 14 grade III, and 44 grade IV). Also, immunohistochemistry was assessed to evaluate the p53 protein expression. In this study, we found that the higher histological grades were statistically associated with TP53 mutations. Some of these mutations, such as TP53 P98T and TP53 G244S, seemed to be a specific marker for the higher grades, and the TP53 E286K mutation appears to be a World Health Organization grade III–IV progression marker. Also, the TP53 P98T mutation, in exon 4, is very likely to be important on the stabilization of the p53 protein, leading to its immunopositivity and it is potentially associated with the TP53 72Pro/Pro genotype.