Clinicopathologic Characteristics of Brain Tumors are Associated with the Presence and Patterns of TP53 Mutations: Evidence from the IARC TP53 Database

Abstract

Biological diversity in the development and progression of brain tumors may be based on the consequences of the nature of the TP53 mutation in the cancer sample. This study was designed to estimate the possible impact of the presence and spectrum of TP53 mutations on clinical variability of brain tumors using the IARC TP53 Database (R17). Somatic and germline mutation patterns differ in brain tumor carriers. The most frequent mutation in sporadic brain tumors is mutation R273C, which is relatively rare in grade 4 tumors compared with lower-grade tumors (p = 1.2 × 10(-5), OR 0.43, 95% CI 0.29-0.63). Mutations at all hot spots, DNA contact mutations, and mutations in the conserved regions of the TP53 gene are also more common in grade 1-3 tumors than in grade 4 tumors. The frequencies of missense mutations at hotspot codons and DNA contact mutations gradually decrease in all three age groups studied, indicating the role of these mutations in early-onset tumors. The role of TP53 somatic mutations in the development of brain tumors has been elucidated in the individual-participant meta-analysis that provided, for the first time, strong evidence that mean age at the onset of sporadic brain tumor is significantly lower in patients with mutated compared with wild-type TP53 in all groups stratified by tumor grade. The presence and patterns of TP53 mutations are associated mainly with the age at the onset and with the development of less malignant brain tumors. Malignant degeneration of brain tumors may depend on other genetic determinants.