Complete loss of TP53 and RB1 is associated with complex genome and low immune infiltrate in pleomorphic rhabdomyosarcoma

HGG Adv. 2023 Jul 19;4(4):100224. doi: 10.1016/j.xhgg.2023.100224. eCollection 2023 Oct 12.

Abstract

Rhabdomyosarcoma accounts for roughly 1% of adult sarcomas, with pleomorphic rhabdomyosarcoma (PRMS) as the most common subtype. Survival outcomes remain poor for patients with PRMS, and little is known about the molecular drivers of this disease. To better characterize PRMS, we performed a broad array of genomic and immunostaining analyses on 25 patient samples. In terms of gene expression and methylation, PRMS clustered more closely with other complex karyotype sarcomas than with pediatric alveolar and embryonal rhabdomyosarcoma. Immune infiltrate levels in PRMS were among the highest observed in multiple sarcoma types and contrasted with low levels in other rhabdomyosarcoma subtypes. Lower immune infiltrate was associated with complete loss of both TP53 and RB1. This comprehensive characterization of the genetic, epigenetic, and immune landscape of PRMS provides a roadmap for improved prognostications and therapeutic exploration.

Keywords: Complex karyotype; Pleomorphic rhabdomyosarcoma; Rhabdomyosarcoma; Sarcoma; TP53.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Child
  • Genomics
  • Humans
  • Protein Processing, Post-Translational
  • Retinoblastoma Binding Proteins / genetics
  • Rhabdomyosarcoma* / genetics
  • Rhabdomyosarcoma, Embryonal* / genetics
  • Soft Tissue Neoplasms*
  • Tumor Suppressor Protein p53 / genetics
  • Ubiquitin-Protein Ligases

Substances

  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • RB1 protein, human
  • Ubiquitin-Protein Ligases
  • Retinoblastoma Binding Proteins