The clinicopathological and prognostic significance of TP53 alteration in K27M mutated gliomas: an individual-participant data meta-analysis

Neurol Sci. 2018 Jul;39(7):1191-1201. doi: 10.1007/s10072-018-3407-1. Epub 2018 Apr 12.

Abstract

This study aimed to investigate the impact of TP53 alteration on survival and clinicopathological features of glioma patients with H3K27M mutations. An individual-participant-data (IPD) meta-analysis was performed to investigate the impact of TP53 alteration on survival and clinicopathological features of patients with H3K27M mutations. Three hundred thirty-one individual records from 12 eligible glioma studies involving the H3K27M mutation were finally included in our meta-analysis, and a pooled hazard ratio (HR) of 1.53 (95%CI, 1.10-2.11; P = 0.01) indicated that TP53 alterations were associated with a shorter overall survival. The pooled odds ratios (ORs) indicated that TP53 alterations were significantly associated with the age at diagnosis ≥ 7 years (OR = 1.97, 95%CI = 1.15-3.38, P = 0.01), the status of histone H3.3 mutations (OR = 9.15, 95%CI = 4.18-20.06, P < 0.00001), and high WHO grade histology (III + IV) (OR = 2.70, 95%CI = 1.33-5.48, P = 0.006). However, no association was found between TP53 alterations and gender or tumor location. This IPD meta-analysis suggests that TP53 alteration is a valuable predictor for the prognosis of patients with H3K27M mutated gliomas. TP53 alteration may be used for identifying a subset of patients who potentially benefit from targeted reactivation of TP53 activity.

Keywords: Glioma; Meta-analysis; Survival; TP53.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / mortality*
  • Brain Neoplasms / pathology
  • Glioma / diagnosis
  • Glioma / genetics*
  • Glioma / mortality*
  • Glioma / pathology
  • Histones / genetics
  • Humans
  • Mutation*
  • Prognosis
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • Histones
  • TP53 protein, human
  • Tumor Suppressor Protein p53