Primary Astrocytic Tumours and Paired Recurrences have Similar Biological Features in IDH1, TP53 and TERTp Mutation and MGMT, ATRX Loss

Sci Rep. 2017 Oct 12;7(1):13038. doi: 10.1038/s41598-017-13272-9.

Abstract

Astrocytic tumours are the most common type of primary malignant brain tumour. Most astrocytic tumours will recur at some point after surgery. Currently, the combination of radiotherapy and chemotherapy does not prevent the recurrence of astrocytic tumours. In this study, we investigated the consistency in isocitrate dehydrogenase 1 (IDH1), tumour protein p53 (TP53) and telomerase reverse transcriptase promoter (TERTp) mutations during astrocytic tumour recurrence. We also evaluated the protein loss of O-6-methylguanine-DNA methyltransferase (MGMT) and alpha-thalassemia/mental retardation, X-linked (ATRX) during disease recurrence. We then determined the prognostic significance of these findings in terms of progression-free survival (PFS) using Kaplan-Meier analysis and Cox regression models. Our results showed that in most cases, IDH1, TP53 and TERTp mutation status and MGMT and ATRX protein expression levels were stable during recurrence, which may indicate that these alterations occurred early in astrocytic tumour development. Furthermore, in IDH1 wild type group, the patients who were negative for MGMT and had a low Ki67 index showed a longer PFS. Therefore, we suggest that IDH1 mutation combined with MGMT expression level and Ki67 index might be an effective biomarker panel for evaluating the PFS of patients with astrocytic tumours.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Astrocytoma / genetics*
  • Astrocytoma / pathology
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics
  • Glioma / pathology
  • Humans
  • Isocitrate Dehydrogenase / genetics*
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Mutation Rate
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / pathology
  • Prognosis
  • Progression-Free Survival
  • Proportional Hazards Models
  • Telomerase / genetics*
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Proteins / genetics*
  • X-linked Nuclear Protein / genetics*
  • Young Adult

Substances

  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • DNA Modification Methylases
  • MGMT protein, human
  • TERT protein, human
  • Telomerase
  • ATRX protein, human
  • X-linked Nuclear Protein
  • DNA Repair Enzymes