Language

English

Publication Date

9-5-2024

Journal

Cell

DOI

10.1016/j.cell.2024.06.023

PMID

38986619

Abstract

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.

Keywords

Ependymoma, Humans, Infratentorial Neoplasms, Genome, Human, Infant, Brain Neoplasms, Child, Male, Female, 3D genome. PFA. TULIPs. brain tumor. childhood cancer. chromatin. ependymoma. epigenomics. genomics. transcriptomics

Published Open-Access

yes

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