Medulloblastoma in Adults: Cytogenetic Phenotypes Identify Prognostic Subgroups. Issue 5 (15th April 2021)

• Record Type: Journal Article
• Authors: Goschzik, Tobias; zur Muehlen, Anja; Doerner, Evelyn; Waha, Andreas; Friedrich, Carsten; Hau, Peter; Pietsch, Torsten
• Is Part Of: Journal of neuropathology and experimental neurology. Volume 80:Issue 5(2021)
• Page Start: 419
• Page End: 430
• Publication Date: 2021-04-15
• Subjects: Adults -- Medulloblastoma -- Mutations -- Whole chromosomal aberrations; Neurology -- Diseases -- Periodicals; Neurology -- Diseases -- Physiopathology -- Periodicals; 616.8047
• DOI: 10.1093/jnen/nlab020
• Languages: English
• ISSNs: 0022-3069

Abstract

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 PTCH1 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 TP53 wt 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- TP53 wt-MBs and p = 0.048 for non-WNT/non-SHH-MBs).