TULIPs decorate the three-dimensional genome of PFA ependymoma,Cell

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TULIPs decorate the three-dimensional genome of PFA ependymoma
Cell ( IF 45.5 ) Pub Date : 2024-07-09 , DOI: 10.1016/j.cell.2024.06.023
Michael J Johnston ₁ , John J Y Lee ₂ , Bo Hu ₃ , Ana Nikolic ₄ , Elham Hasheminasabgorji ₄ , Audrey Baguette ₅ , Seungil Paik ₁ , Haifen Chen ₆ , Sachin Kumar ₇ , Carol C L Chen ₆ , Selin Jessa ₅ , Polina Balin ₂ , Vernon Fong ₂ , Melissa Zwaig ₆ , Kulandaimanuvel Antony Michealraj ₇ , Xun Chen ₈ , Yanlin Zhang ₉ , Srinidhi Varadharajan ₁₀ , Pierre Billon ₁₁ , Nikoleta Juretic ₁₂ , Craig Daniels ₁₃ , Amulya Nageswara Rao ₁₄ , Caterina Giannini ₁₄ , Eric M Thompson ₁₅ , Miklos Garami ₁₆ , Peter Hauser ₁₆ , Timea Pocza ₁₆ , Young Shin Ra ₁₇ , Byung-Kyu Cho ₁₈ , Seung-Ki Kim ₁₈ , Kyu-Chang Wang ₁₈ , Ji Yeoun Lee ₁₈ , Wieslawa Grajkowska ₁₉ , Marta Perek-Polnik ₂₀ , Sameer Agnihotri ₂₁ , Stephen Mack ₁₀ , Benjamin Ellezam ₂₂ , Alex Weil ₂₃ , Jeremy Rich ₂₄ , Guillaume Bourque ₂₅ , Jennifer A Chan ₂₆ , V Wee Yong ₂₇ , Mathieu Lupien ₂₈ , Jiannis Ragoussis ₂₅ , Claudia Kleinman ₂₉ , Jacek Majewski ₆ , Mathieu Blanchette ₃₀ , Nada Jabado ₃₁ , Michael D Taylor ₃₂ , Marco Gallo ₃₃

Affiliation

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.
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 Human Genetics, McGill University, Montreal, QC H2A 1B1, Canada; Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
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.
Quantitative Life Sciences, McGill University, Montreal, QC H3A 1B9, Canada.
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.
Department of Anatomy and Cell Biology, Kyoto University, Kyoto 606-8501, Japan.
School of Computer Science, McGill University, Montreal, QC H3A 2A7, Canada.
Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
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.
Department of Pediatrics, McGill University and The Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
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.
Pediatric Hematology-Oncology, Mayo Clinic, Rochester, MN 55905, USA.
Department of Neurosurgery, Duke University Medical Center, Durham, NC 27710, USA.
Department of Pediatrics, Semmelweis University, H-1094 Budapest, Hungary.
Department of Neurosurgery, University of Ulsan, Asan Medical Center, Seoul 05505, South Korea.
Department of Neurosurgery, Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul 30322, South Korea.
Department of Pathology, The Children's Memorial Health Institute, University of Warsaw, 04-730 Warsaw, Poland.
Department of Oncology, The Children's Memorial Health Institute, University of Warsaw, 04-730 Warsaw, Poland.
Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, United States of America.
Department of Pathology, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal, QC H3T 1C5, Canada.
Department of Pediatric Neurosurgery, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal, QC H3T 1C5, Canada.
University of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, PA 15213, USA; Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
Department of Human Genetics, McGill University, Montreal, QC H2A 1B1, Canada; McGill Genome Centre, Montreal, QC H3A 0G1, Canada.
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.
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.
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.
Department of Human Genetics, McGill University, Montreal, QC H2A 1B1, Canada; Lady Davis Research Institute, Jewish General Hospital, Montreal, QC H3T 1E2, Canada.
Quantitative Life Sciences, McGill University, Montreal, QC H3A 1B9, Canada; School of Computer Science, McGill University, Montreal, QC H3A 2A7, Canada.
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.
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.
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.

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.

中文翻译：

TULIPs 装饰 PFA 室管膜瘤的三维基因组

后颅窝 A 组 (PFA) 室管膜瘤是一种在婴儿和幼儿中诊断出的致命脑癌。 PFA 线性基因组中缺乏驱动事件，导致我们在其 3D 基因组中搜索特征。在这里，我们重建了多种儿童肿瘤类型的 3D 基因组，并发现了 PFA 中的全局拓扑结构，该拓扑结构与多种人体组织中的干细胞和祖细胞高度相似。 PFA 中独有的一个显着特征是 PFA (TULIP) 中的 B 型超长程相互作用，这些区域沿着线性基因组相距很远，在 3D 核空间中以惊人的强度相互作用。 TULIP 存在于所有 PFA 样本中，并在可预测的基因组坐标处重复出现，它们的形成是由 EZHIP 的表达诱导的。 TULIP 在 PFA 样本中的普遍性表明分子原理的保守性可以用于治疗。

更新日期：2024-07-09

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