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


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
Issue number3
StatePublished - Sep 1 2023

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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