Goschzik, Tobias and Zur Muehlen, Anja and Doerner, Evelyn and Waha, Andreas and Friedrich, Carsten and Hau, Peter and Pietsch, Torsten (2021) Medulloblastoma in Adults: Cytogenetic Phenotypes Identify Prognostic Subgroups. JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 80 (5). pp. 419-430. ISSN 0022-3069, 1554-6578
Full text not available from this repository. (Request a copy)Abstract
Adult medulloblastomas (MB) are rare. We investigated the genetic landscape and prognostic impact of genetic aberrations in a cohort of 117 adult medulloblastomas. Histological features and pathway activation were evaluated at the protein level; 14.5% showed wingless-type activation, 63.3% SHH activation, and 22.2% were classified as non-WNT/non-SHH-MB. Genome-wide copy number analysis was performed by molecular inversion probe array technology. MB-related genes were sequenced in WNT- and SHH-activated MBs. 79.7% of SHH-MBs showed desmoplastic/nodular histology; all other MBs had classic histology. WNT-MBs carried oncogenic CTNNB1 mutations in 88.2% and had monosomy 6 in 52.9%. In SHH-MBs, TERT promoter mutations occurred in 97%, mutations in PTCHI in 38.2%, SMO in 15.5%, SUFU in 7.4%, and TP53-mutations in 4.1%. In all, 84.6% of non-WNT/non-SHH-MBs had an isochromosome 17q. A whole chromosomal aberration (WCA) signature was present in 45.1% of SHH-TP53-wild type (wt)-MBs and 65.4% of non-WNT/non-SHH-MBs. In 98 cases with survival data, WNT-MBs had a 5-year overall survival (OS) of 68.6%. SHH-MBs TP53wt type and non-WNT/non-SHH-MBs showed 5-year OS of 80.4% and 70.8%, respectively. TP53-mutant SHH-MBs represented a prognostically unfavorable entity; all patients died within 5 years. Patients with a WCA signature showed significantly increased OS (p = 0.011 for SHH-TP53wt-MBs and p = 0.048 for non-WNT/non-SHH-MBs).
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MOLECULAR SUBGROUPS; RECURRENT; CANCER; RISK; Adults; Medulloblastoma; Mutations; Whole chromosomal aberrations |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 06 Sep 2022 13:57 |
| Last Modified: | 06 Sep 2022 13:57 |
| URI: | https://pred.uni-regensburg.de/id/eprint/46744 |
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