The 3D chromatin landscape of rhabdomyosarcoma

Meng Wang, Prethish Sreenivas, Benjamin D. Sunkel, Long Wang, Myron Ignatius, Benjamin Z. Stanton

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Rhabdomyosarcoma (RMS) is a pediatric soft tissue cancer with a lack of precision therapy options for patients. We hypothesized that with a general paucity of known mutations in RMS, chromatin structural driving mechanisms are essential for tumor proliferation. Thus, we carried out high-depth in situ Hi-C in representative cell lines and patient-derived xenografts (PDXs) to define chromatin architecture in each major RMS subtype. We report a comprehensive 3D chromatin structural analysis and characterization of fusion-positive (FP-RMS) and fusion-negative RMS (FN-RMS). We have generated spike-in in situ Hi-C chromatin interaction maps for the most common FP-RMS and FN-RMS cell lines and compared our data with PDX models. In our studies, we uncover common and distinct structural elements in large Mb-scale chromatin compartments, tumor-essential genes within variable topologically associating domains and unique patterns of structural variation. Our high-depth chromatin interactivity maps and comprehensive analyses provide context for gene regulatory events and reveal functional chromatin domains in RMS.

Original languageEnglish (US)
Article numberzcad028
JournalNAR Cancer
Volume5
Issue number3
DOIs
StatePublished - Sep 1 2023

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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