Multi-omics analysis of intertumoral heterogeneity within medulloblastoma uncharted-pathway subtypes.
Brain Tumor Pathol
; 38(3): 234-242, 2021 Jul.
Article
en En
| MEDLINE
| ID: mdl-34180021
ABSTRACT
Medulloblastoma is a common pediatric malignant brain tumor. There were four consensus molecular subgroups (WNT, SHH, Group3 and Group4). Group 3 and Group 4 tumors exhibited a great degree of transcriptional overlap, and were neither derived from exact pathway aberration. We investigated transcriptional and chromatin accessibility of medulloblastoma by multi-omics single-cell analysis. Our work identified inter- and intra-tumoral heterogeneity within the Group 3, Group 4 and Group 3/4 intermediate subgroups. Unsupervised cluster of each tumor identified 9 cell clusters with transcriptional profiles and 6 cell clusters with chromatin accessibility profiles. OTX2 had the highest activity and expression level across the clusters in a special cluster based on open chromatin single-cell profilings. We identified multiple genes as a significant targeted gene within the OTX2 target genes, which made sense in prognosis. We analyzed the copy-number-variations which presented with expected subgroup distribution from transcriptional and chromatin accessibility profiles. Collectively, these data provide novel insights into Group 3 and Group 4 medulloblastoma and provide a potential therapeutic target.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Encefálicas
/
Meduloblastoma
Tipo de estudio:
Prognostic_studies
Límite:
Child
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Brain Tumor Pathol
Asunto de la revista:
CEREBRO
/
NEOPLASIAS
/
PATOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
China