guest ::
| Home > Publications database > Integrated molecular analysis of adult Sonic Hedgehog (SHH)-activated medulloblastomas reveals two clinically relevant tumor subsets with VEGFA as potent prognostic indicator. |
| Home > Publications database > Integrated molecular analysis of adult Sonic Hedgehog (SHH)-activated medulloblastomas reveals two clinically relevant tumor subsets with VEGFA as potent prognostic indicator. |
| Journal Article | DKFZ-2021-00383 |
; ; ; ; ; ; ; ; ; ; ; ; ;
2021
Oxford Univ. Press
Oxford
This record in other databases: 
Please use a persistent id in citations: doi:10.1093/neuonc/noab031
Abstract: Up to now, adult medulloblastoma (MB) patients are treated according to the protocols elaborated for pediatric MB although these tumors are different in terms of clinical outcomes and biology. Approximately 70% of adult MB disclose a Sonic Hedgehog (SHH) molecular signature in contrast to about 30% in pediatric cohorts. In addition, adult SHH-MB (aSHH-MB) are clinically heterogeneous but there is consensus neither on their optimal treatment nor on risk stratification. Thus, the identification of clinically relevant molecular subsets of aSHH-MB and identification of potential treatment targets remains inconclusive.We analyzed 96 samples of institutionally diagnosed aSHH-MB through genome-wide DNA methylation profiling, targeted DNA sequencing and RNA sequencing to identify molecular subcategories of these tumors and assess their prognostic significance.We defined two aSHH-MB numerically comparable epigenetic subsets with clinical and molecular variability. The subset 'aSHH-MBI' (46/48%) was associated with PTCH1/SMO (54%/46%) mutations, 'neuronal' transcriptional signatures, and favorable outcomes after combined radio-chemotherapy (5-year PFS = 80% and OS = 92%). The clinically unfavorable 'aSHH-MBII' subset (50/52%; 5-year PFS = 24% and OS = 45%) disclosed GLI2 amplifications (8%), loss of 10q (22%), and gene expression signatures associated with angiogenesis and embryonal development. aSHH-MBII tumors revealed strong and ubiquitous expression of VEGFA both at transcript and protein levels that was correlated with unfavorable outcome.1. The histologically uniform aSHH-MB cohort exhibits clear molecular heterogeneity separating these tumors into two molecular subsets (aSHH-MBI and aSHH-MBII), which are associated with different cytogenetics, mutational landscapes, gene expression signatures, and clinical course. 2. VEGFA appears to be a promising biomarker to predict clinical course, which needs further prospective validation as its potential role in the pathogenesis of this subset.
Keyword(s): Adult ; Medulloblastoma ; SHH ; VEGFA ; prognosis ; transcriptome
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Essential Science Indicators ; IF >= 10 ; JCR ; Nationallizenz
; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
|
The record appears in these collections: |
