Publication Date
12-5-2024
Journal
American Journal of Human Genetics
DOI
10.1016/j.ajhg.2024.10.003
PMID
39481374
PMCID
PMC11639096
PubMedCentral® Posted Date
10-30-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Medulloblastoma, Humans, Cerebellar Neoplasms, DNA Methylation, Genome, Human, Gene Expression Regulation, Neoplastic, Transcriptome, Animals, Male, Female, Mice, Hi-C, 3D genome, transcriptome, medulloblastoma, cancer, CNS tumor
Abstract
Four main medulloblastoma (MB) molecular subtypes have been identified based on transcriptional, DNA methylation, and genetic profiles. However, it is currently not known whether 3D genome architecture differs between MB subtypes. To address this question, we performed in situ Hi-C to reconstruct the 3D genome architecture of MB subtypes. In total, we generated Hi-C and matching transcriptome data for 28 surgical specimens and Hi-C data for one patient-derived xenograft. The average resolution of the Hi-C maps was 6,833 bp. Using these data, we found that insulation scores of topologically associating domains (TADs) were effective at distinguishing MB molecular subgroups. TAD insulation score differences between subtypes were globally not associated with differential gene expression, although we identified few exceptions near genes expressed in the lineages of origin of specific MB subtypes. Our study therefore supports the notion that TAD insulation scores can distinguish MB subtypes independently of their transcriptional differences.
Graphical Abstract
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Mental and Social Health Commons, Neurology Commons, Neurosciences Commons, Oncology Commons
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