3D genome topology distinguishes molecular subgroups of medulloblastoma
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.
Authors
- Marco Gallo (ORCID: https://orcid.org/0000-0002-8451-8207)
- Melissa Zwaig (ORCID: https://orcid.org/0000-0001-9565-838X)
- Raúl A. Suárez
- Hamza Farooq (ORCID: https://orcid.org/0000-0001-5311-4368)
- Jiannis Ragoussis (ORCID: https://orcid.org/0000-0002-8515-0934)
- John J. Y. Lee (ORCID: https://orcid.org/0000-0002-7967-3384)
- Subhi Talal Younes
- Nikoleta Juretic (ORCID: https://orcid.org/0000-0001-8265-8305)
- Michael J. Johnston (ORCID: https://orcid.org/0000-0001-6769-6311)
- Nada Jabado (ORCID: https://orcid.org/0000-0003-2485-3692)
- William A. Weiss (ORCID: https://orcid.org/0000-0003-2230-9132)
- Huey‐Miin Chen (ORCID: https://orcid.org/0000-0002-1939-3487)
- Michael D. Taylor (ORCID: https://orcid.org/0000-0001-7009-3466)
Institutions
- University of Calgary (CA)
- University of California, San Francisco (US)
- Hospital for Sick Children (CA)
- McGill University Health Centre (CA)
- McGill Genome Centre (CA)
- Texas Children's Hospital (US)
- Children's Cancer Center (US)
- UCSF Helen Diller Family Comprehensive Cancer Center (US)
- McGill University (CA)
Publication Details
- Journal
- The American Journal of Human Genetics
- Published
- 2024-10-31
- DOI
- https://doi.org/10.1016/j.ajhg.2024.10.003
- Citations
- 1
- Primary Topic
- Genomics and Chromatin Dynamics
- Type
- article
- Field-Weighted Citation Impact
- 0.23
Funders
- Norges Idrettshøgskole
- Canadian Institutes of Health Research