Abstract
Purpose: Magnetic resonance (MR) imaging biomarkers can assist in the non-invasive assessment of the genetic status in glioblastomas (GBMs). Telomerase reverse transcriptase (TERT) promoter mutations are associated with a negative prognosis. This study was performed to identify MR imaging biomarkers to forecast the TERT mutation status. Methods: Pre-operative MRIs of 64/67 genetically confirmed primary GBM patients (51/67 TERT-mutated with rs2853669 polymorphism) were analyzed according to Visually AcceSAble Rembrandt Images (VASARI) (https://wiki.cancerimagingarchive.net/display/Public/VASARI+Research+Project) imaging criteria by three radiological raters. TERT mutation and O6-methylguanine-DNA methyltransferase (MGMT) hypermethylation data were obtained through direct and pyrosequencing as described in a previous study. Clinical data were derived from a prospectively maintained electronic database. Associations of potential imaging biomarkers and genetic status were assessed by Fisher and Mann-Whitney U tests and stepwise linear regression. Results: No imaging biomarkers could be identified to predict TERT mutational status (alone or in conjunction with TERT promoter polymorphism rs2853669 AA-allele). TERT promoter mutations were more common in patients with tumor-associated seizures as first symptom (26/30 vs. 25/37, p = 0.07); these showed significantly smaller tumors [13.1 (9.0–19.0) vs. 24.0 (16.6–37.5) all cm3; p = 0.007] and prolonged median overall survival [17.0 (11.5–28.0) vs. 9.0 (4.0–12.0) all months; p = 0.02]. TERT-mutated GBMs were underrepresented in the extended angularis region (p = 0.03), whereas MGMT-methylated GBMs were overrepresented in the corpus callosum (p = 0.03) and underrepresented temporomesially (p = 0.01). Conclusion: Imaging biomarkers for prediction of TERT mutation status remain weak and cannot be derived from the VASARI protocol. Tumor-associated seizures are less common in TERT mutated glioblastomas.
Original language | English |
---|---|
Pages (from-to) | 1223-1231 |
Number of pages | 9 |
Journal | Neuroradiology |
Volume | 59 |
Issue number | 12 |
DOIs | |
Publication status | Published - 1 Dec 2017 |
Externally published | Yes |
Keywords
- Adult
- Aged
- Aged, 80 and over
- Biomarkers, Tumor
- Brain Neoplasms/genetics
- Female
- Glioblastoma/genetics
- Humans
- Magnetic Resonance Imaging/methods
- Male
- Middle Aged
- Mutation
- Polymorphism, Single Nucleotide
- Prognosis
- Promoter Regions, Genetic
- Telomerase/genetics