MRI Features Associated with TERT Promoter Mutation Status in Glioblastoma

J Neuroimaging. 2019 May;29(3):357-363. doi: 10.1111/jon.12596. Epub 2019 Jan 15.

Abstract

Background and purpose: Telomerase reverse transcriptase (TERT) promoter mutations are associated with worse prognosis in glioblastoma. The purpose of this study was to evaluate whether TERT mutation status was associated with specific morphologic and quantitative imaging features.

Methods: Twenty-nine patients with isocitrate dehydrogenase 1/2-wildtype glioblastoma (13 TERT-wildtype, 16 TERT-mutated), who underwent preoperative magnetic resonance (MR) imaging were included in this retrospective study. Qualitative imaging phenotypes were evaluated using the Visually Accessible Rembrandt Images (VASARIs) feature set. Histogram analysis of apparent diffusion coefficient (ADC) and dynamic contrast-enhanced MR perfusion values were performed on enhancing tumor volumes-of-interest, and differences between TERT-wildtype and TERT-mutated tumors were assessed.

Results: VASARI analysis demonstrated that the majority of morphologic features were not significantly different between TERT-wildtype and TERT-mutated tumors, although a higher proportion of TERT-wildtype tumors featured nonenhancing tumor crossing midline (P = .014). TERT-mutated tumors demonstrated lower median rate constant kep (.38 vs. .76, P = .03) and lower median volume transfer coefficient Ktrans (.13 vs. .31, P = .02). There was no significant difference in median plasma volume vp (P = .92) or ADC values (P = .66) between the two groups. We further found a significant interaction between median kep and Ktrans and TERT status, respectively, suggesting greater risk of death with increasing blood-brain barrier dysfunction in TERT-mutated but not in TERT-wildtype tumors.

Conclusion: Our study demonstrates evidence of altered permeability metrics associated with TERT mutation in glioblastoma, laying the foundation for future prospective studies assessing implications for therapeutic management and clinical outcomes.

Keywords: TERT mutation; glioblastoma; radiogenomics.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Brain / diagnostic imaging*
  • Brain Neoplasms / diagnostic imaging*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Female
  • Glioblastoma / diagnostic imaging*
  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Mutation*
  • Promoter Regions, Genetic
  • Prospective Studies
  • Retrospective Studies
  • Telomerase / genetics*
  • Tumor Burden
  • Young Adult

Substances

  • TERT protein, human
  • Telomerase