gms | German Medical Science

73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

29.05. - 01.06.2022, Köln

Genomic characterisation of IDH-Wildtype Glioblastoma in different age groups

Genomische Charakterisierung der IDH-Wildtyp Glioblastome in verschiedenen Altersgruppen

Meeting Abstract

  • presenting/speaker Sven Richter - Carl Gustav Carus Universitätsklinikum, TU Dresden, Klinik und Poliklinik für Neurochirurgie, Dresden, Deutschland
  • Sebastian Stasik - Carl Gustav Carus Universitätsklinikum, TU Dresden, Medizinische Klinik I, Dresden, Deutschland
  • Gabriele Schackert - Carl Gustav Carus Universitätsklinikum, TU Dresden, Klinik und Poliklinik für Neurochirurgie, Dresden, Deutschland
  • Christian Thiede - Carl Gustav Carus Universitätsklinikum, TU Dresden, Medizinische Klinik I, Dresden, Deutschland
  • Dietmar Krex - Carl Gustav Carus Universitätsklinikum, TU Dresden, Klinik und Poliklinik für Neurochirurgie, Dresden, Deutschland
  • Tareq Juratli - Carl Gustav Carus Universitätsklinikum, TU Dresden, Klinik und Poliklinik für Neurochirurgie, Dresden, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie. Köln, 29.05.-01.06.2022. Düsseldorf: German Medical Science GMS Publishing House; 2022. DocV223

doi: 10.3205/22dgnc216, urn:nbn:de:0183-22dgnc2164

Veröffentlicht: 25. Mai 2022

© 2022 Richter et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Objective: IDH-wildtype Glioblastomas (IDH-wt GBM) are molecularly heterogeneous tumors with poor prognosis and a high incidence in the elderly population. However, IDH-wt GBM may occur in young patients and are associated with a relatively better prognosis. Here, we sought to explore whether IDH-wt GBM have an age-specific molecular signature that correlates with patients' outcome.

Methods: We performed a comprehensive molecular characterization of 55 IDH-wt GBM, using Whole Exome Sequencing (WES) in addition to Sanger Sequencing for the TERT-promoter region. Moreover, progression- and overall survival (PFS, OS) data, clinical- and tumor features were collected.

Results: The patients’ median age at diagnosis (AAD) was 58 yrs. (range: 22.9-70.8 yrs.). We divided our study cohort into three subgroups based on quartiles of AAD for further analysis: Group A: 22.9-40.4 yrs. (Q1), Group B: 44.5-71.0 yrs. (Q2-3) and Group C: 72.7-79.8 yrs. (Q4). The median OS for all patients was 15.9 Mo. with a PFS of 9.5 Mo. The median tumor volume at initial presentation was 43.8 cm3 and correlated with AAD: 63.6 cm3 (Group A) vs. 41.2 cm3 (Group C).

We identified a median of 32 mutations per tumor. Exome and Sanger sequencing detected frequent alterations on TERT-promoter (76.4%) and EGFR (90.9% gain, 50.1% amplification, 29.1% mutation). Chromosome 7 gain (92.7%) and Chromosome 10 deletion (85.5%) occurred significantly less in younger patients (Group A vs. Groups B+C; p=0.037, p=0.013). However, other individual alterations did not correlate with AAD. Via clustering of various alterations (e.g. TP53, PDGFRA, ATRX), we found an association between a proneural GBM signature with younger AAD (p=0.036). AAD itself had an independent impact on OS: 21.5 Mo. (Group A) vs. 10.1 Mo. (Group C). Moreover, we described TET1-deletions on Chr. 10 in 90.1% of cases, which was not previously described in IDH-wt GBM. Bi-allelic TET1-deletions (32.7%) with concurrent EGFR-amplification had a significant impact on patient’s outcome (OS 12.2 Mo. vs. 17.6 Mo.; p=0.013).

Conclusion: Even though GBM signatures showed subtle association with AAD, our data suggests that there is no age-specific molecular pattern for IDH-wt GBM. The heterogeneity of IDH-wt GBM persists throughout the entire spectrum of AAD, leaving the cause of better prognosis at younger age unclear on a molecular explanatory approach. Finally, TET1-deletion may represent a relevant alteration in IDH-wt GBM.