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| Status |
Public on Jul 30, 2019 |
| Title |
Single cell RNA-seq analysis of medulloblastoma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Medulloblastoma is a malignant childhood cerebellar tumour comprised of distinct molecular subgroups. Whereas genomic characteristics of these subgroups are well defined, the extent to which cellular diversity underlies their divergent biology and clinical behaviour remains largely unexplored. We used single-cell transcriptomics to investigate intra- and inter-tumoural heterogeneity in twenty-five medulloblastomas spanning all molecular subgroups. WNT, SHH, and Group 3 tumours comprised subgroup-specific undifferentiated and differentiated neuronal-like malignant populations, whereas Group 4 tumours were exclusively comprised of differentiated neuronal-like neoplastic cells. SHH tumours closely resembled granule neurons of varying differentiation states that correlated with patient age. Group 3 and Group 4 tumours exhibited a developmental trajectory from primitive progenitor-like to more mature neuronal-like cells, whose relative proportions distinguished these subgroups. Cross-species transcriptomics defined distinct glutamatergic populations as putative cells-of-origin for SHH and Group 4 subtypes. Collectively, these data provide novel insights into the cellular and developmental states underlying subtype-specific medulloblastoma biology.
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| Overall design |
We prospectively obtained fresh surgical resections from a series of twenty-five MB patients, including 23 diagnostic samples and two recurrences, and eleven patient-derived xenograft (PDX) models. Samples were obtained as fresh tumour biopsies from three different treating centers, including LeBonheur Children?s Hospital (n=12), Boston Children?s Hospital (n=4), and Vienna General Hospital (n=9). Patients were predominantly male (19 males vs. 6 females) and ages ranged from 3-17 years (median=9 years). Classic (n=16), large-cell/anaplastic (n=6), and desmoplastic/nodular (n=3) histologies were included in our series and there was an abundance of patients with metastatic disease (16/25, 64%).
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| Contributor(s) |
Hovestadt V, Smith KS, Bihannic L, Filbin MG, Bernstein BE, Suva ML, Northcott PA |
| Citation(s) |
31341285 |
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| Submission date |
Sep 13, 2018 |
| Last update date |
Jul 30, 2019 |
| Contact name |
Volker Hovestadt |
| E-mail(s) |
ncbi@hovestadt.bio
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| Organization name |
Dana-Farber Cancer Institute
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| Department |
Pediatric Oncology
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| Lab |
Hovestadt lab
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| Street address |
360 Longwood Avenue
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (36)
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| Relations |
| BioProject |
PRJNA490728 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE119926_RAW.tar |
120.5 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data provided as supplementary file |
| Raw data not provided for this record |
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