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- Title
Clinical and mutational profiles of adult medulloblastoma groups.
- Authors
Wong, Gabriel Chun-Hei; Li, Kay Ka-Wai; Wang, Wei-Wei; Liu, Anthony Pak-Yin; Huang, Queenie Junqi; Chan, Aden Ka-Yin; Poon, Manix Fung-Man; Chung, Nellie Yuk-Fei; Wong, Queenie Hoi-Wing; Chen, Hong; Chan, Danny Tat Ming; Liu, Xian-Zhi; Mao, Ying; Zhang, Zhen-Yu; Shi, Zhi-Feng; Ng, Ho-Keung
- Abstract
Adult medulloblastomas are clinically and molecularly understudied due to their rarity. We performed molecular grouping, targeted sequencing, and TERT promoter Sanger sequencing on a cohort of 99 adult medulloblastomas. SHH made up 50% of the cohort, whereas Group 3 (13%) was present in comparable proportion to WNT (19%) and Group 4 (18%). In contrast to paediatric medulloblastomas, molecular groups had no prognostic impact in our adult cohort (p = 0.877). Most frequently mutated genes were TERT (including promoter mutations, mutated in 36% cases), chromatin modifiers KMT2D (31%) and KMT2C (30%), TCF4 (31%), PTCH1 (27%) and DDX3X (24%). Adult WNT patients showed enrichment of TP53 mutations (6/15 WNT cases), and 3/6 TP53-mutant WNT tumours were of large cell/anaplastic histology. Adult SHH medulloblastomas had frequent upstream pathway alterations (PTCH1 and SMO mutations) and few downstream alterations (SUFU mutations, MYCN amplifications). TERT promoter mutations were found in 72% of adult SHH patients, and were restricted to this group. Adult Group 3 tumours lacked hallmark MYC amplifications, but had recurrent mutations in KBTBD4 and NOTCH1. Adult Group 4 tumours harboured recurrent mutations in TCF4 and chromatin modifier genes. Overall, amplifications of MYC and MYCN were rare (3%). Since molecular groups were not prognostic, alternative prognostic markers are needed for adult medulloblastoma. KMT2C mutations were frequently found across molecular groups and were associated with poor survival (p = 0.002). Multivariate analysis identified histological type (p = 0.026), metastasis (p = 0.031) and KMT2C mutational status (p = 0.046) as independent prognosticators in our cohort. In summary, we identified distinct clinical and mutational characteristics of adult medulloblastomas that will inform their risk stratification and treatment.
- Publication
Acta Neuropathologica Communications, 2020, Vol 8, Issue 1, p1
- ISSN
2051-5960
- Publication type
Article
- DOI
10.1186/s40478-020-01066-6