TULIPs decorate the three-dimensional genome of PFA ependymoma.

3D genome PFA TULIPs brain tumor childhood cancer chromatin ependymoma epigenomics genomics transcriptomics

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
04 Jul 2024
Historique:
received: 27 08 2021
revised: 26 05 2022
accepted: 18 06 2024
medline: 11 7 2024
pubmed: 11 7 2024
entrez: 10 7 2024
Statut: aheadofprint

Résumé

Posterior fossa group A (PFA) ependymoma is a lethal brain cancer diagnosed in infants and young children. The lack of driver events in the PFA linear genome led us to search its 3D genome for characteristic features. Here, we reconstructed 3D genomes from diverse childhood tumor types and uncovered a global topology in PFA that is highly reminiscent of stem and progenitor cells in a variety of human tissues. A remarkable feature exclusively present in PFA are type B ultra long-range interactions in PFAs (TULIPs), regions separated by great distances along the linear genome that interact with each other in the 3D nuclear space with surprising strength. TULIPs occur in all PFA samples and recur at predictable genomic coordinates, and their formation is induced by expression of EZHIP. The universality of TULIPs across PFA samples suggests a conservation of molecular principles that could be exploited therapeutically.

Identifiants

DOI: 10.1016/j.cell.2024.06.023 PMID: 38986619
pubmed: 38986619
pii: S0092-8674(24)00697-4
doi: 10.1016/j.cell.2024.06.023
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

Michael J Johnston (MJ)

Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.

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.

Bo Hu (B)

Department of Human Genetics, McGill University, Montreal, QC H2A 1B1, Canada; Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.

Ana Nikolic (A)

Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.

Elham Hasheminasabgorji (E)

Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.

Audrey Baguette (A)

Quantitative Life Sciences, McGill University, Montreal, QC H3A 1B9, Canada.

Seungil Paik (S)

Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.

Haifen Chen (H)

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

Sachin Kumar (S)

Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.

Carol C L Chen (CCL)

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

Selin Jessa (S)

Quantitative Life Sciences, McGill University, Montreal, QC H3A 1B9, Canada.

Polina Balin (P)

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.

Vernon Fong (V)

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.

Kulandaimanuvel Antony Michealraj (KA)

Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.

Xun Chen (X)

Department of Anatomy and Cell Biology, Kyoto University, Kyoto 606-8501, Japan.

Yanlin Zhang (Y)

School of Computer Science, McGill University, Montreal, QC H3A 2A7, Canada.

Srinidhi Varadharajan (S)

Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.

Pierre Billon (P)

Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.

Nikoleta Juretic (N)

Department of Pediatrics, McGill University and The Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada.

Craig Daniels (C)

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.

Amulya Nageswara Rao (AN)

Pediatric Hematology-Oncology, Mayo Clinic, Rochester, MN 55905, USA.

Caterina Giannini (C)

Pediatric Hematology-Oncology, Mayo Clinic, Rochester, MN 55905, USA.

Eric M Thompson (EM)

Department of Neurosurgery, Duke University Medical Center, Durham, NC 27710, USA.

Miklos Garami (M)

Department of Pediatrics, Semmelweis University, H-1094 Budapest, Hungary.

Peter Hauser (P)

Department of Pediatrics, Semmelweis University, H-1094 Budapest, Hungary.

Timea Pocza (T)

Department of Pediatrics, Semmelweis University, H-1094 Budapest, Hungary.

Young Shin Ra (YS)

Department of Neurosurgery, University of Ulsan, Asan Medical Center, Seoul 05505, South Korea.

Byung-Kyu Cho (BK)

Department of Neurosurgery, Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul 30322, South Korea.

Seung-Ki Kim (SK)

Department of Neurosurgery, Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul 30322, South Korea.

Kyu-Chang Wang (KC)

Department of Neurosurgery, Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul 30322, South Korea.

Ji Yeoun Lee (JY)

Department of Neurosurgery, Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul 30322, South Korea.

Wieslawa Grajkowska (W)

Department of Pathology, The Children's Memorial Health Institute, University of Warsaw, 04-730 Warsaw, Poland.

Marta Perek-Polnik (M)

Department of Oncology, The Children's Memorial Health Institute, University of Warsaw, 04-730 Warsaw, Poland.

Sameer Agnihotri (S)

Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, United States of America.

Stephen Mack (S)

Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.

Benjamin Ellezam (B)

Department of Pathology, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal, QC H3T 1C5, Canada.

Alex Weil (A)

Department of Pediatric Neurosurgery, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal, QC H3T 1C5, Canada.

Jeremy Rich (J)

University of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, PA 15213, USA; Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.

Guillaume Bourque (G)

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

Jennifer A Chan (JA)

Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.

V Wee Yong (VW)

Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.

Mathieu Lupien (M)

Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada; Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada.

Jiannis Ragoussis (J)

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

Claudia Kleinman (C)

Department of Human Genetics, McGill University, Montreal, QC H2A 1B1, Canada; Lady Davis Research Institute, Jewish General Hospital, Montreal, QC H3T 1E2, Canada.

Jacek Majewski (J)

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

Mathieu Blanchette (M)

Quantitative Life Sciences, McGill University, Montreal, QC H3A 1B9, Canada; School of Computer Science, McGill University, Montreal, QC H3A 2A7, Canada.

Nada Jabado (N)

Department of Human Genetics, McGill University, Montreal, QC H2A 1B1, Canada; Department of Pediatrics, McGill University and 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. Electronic address: nada.jabado@mcgill.ca.

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)

Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Department of Biochemistry and Molecular Biology, 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