3D genome topology distinguishes molecular subgroups of medulloblastoma.

3D genome CNS tumor Hi-C cancer medulloblastoma transcriptome

Journal

American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475

Informations de publication

Date de publication:
22 Oct 2024
Historique:
received: 10 06 2024
revised: 03 10 2024
accepted: 04 10 2024
medline: 1 11 2024
pubmed: 1 11 2024
entrez: 31 10 2024
Statut: aheadofprint

Résumé

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.

Identifiants

DOI: 10.1016/j.ajhg.2024.10.003 PMID: 39481374
pubmed: 39481374
pii: S0002-9297(24)00372-0
doi: 10.1016/j.ajhg.2024.10.003
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

John J Y Lee (JJY)

The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 1L7, Canada.

Michael J Johnston (MJ)

Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.

Hamza Farooq (H)

The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 1L7, Canada.

Huey-Miin Chen (HM)

Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Cancer and Hematology Center, Texas Children's Hospital, Houston, TX 77030, USA.

Subhi Talal Younes (ST)

Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Cancer and Hematology Center, Texas Children's Hospital, Houston, TX 77030, USA.

Raul Suarez (R)

The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 1L7, Canada.

Melissa Zwaig (M)

Department of Human Genetics, McGill University, Montreal, QC H2A 1B1, Canada.

Nikoleta Juretic (N)

Department of Human Genetics, McGill University, Montreal, QC H2A 1B1, Canada; Department of Pediatrics, McGill University, The Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada; Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, QC H3A 3J1, Canada.

William A Weiss (WA)

Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurosurgery, University of California, San Francisco, San Francisco, CA 94143, USA; Brain Tumor Research Center, and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA.

Jiannis Ragoussis (J)

Department of Human Genetics, McGill University, Montreal, QC H2A 1B1, Canada; McGill Genome Centre, Montreal, QC H3A 0G1, Canada.

Nada Jabado (N)

Department of Human Genetics, McGill University, Montreal, QC H2A 1B1, Canada; Department of Pediatrics, McGill University, The Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada; Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, QC H3A 3J1, Canada.

Michael D Taylor (MD)

The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 1L7, Canada; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Cancer and Hematology Center, Texas Children's Hospital, Houston, TX 77030, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: michael.taylor@bcm.edu.

Marco Gallo (M)

Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Cancer and Hematology Center, Texas Children's Hospital, Houston, TX 77030, USA; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: marco.gallo@bcm.edu.

Classifications MeSH