Complete Loss of TP53 and RB1 Is Associated With Complex Genome and Low Immune Infiltrate in Pleomorphic Rhabdomyosarcoma

Authors

Hannah C Beird
Chia-Chin Wu
Michael Nakazawa
Davis Ingram
Joseph R Daniele
Rossana Lazcano
Latasha Little
Christopher Davies
Najat C Daw
Khalida Wani
Wei-Lien Wang
Xingzhi Song
Curtis Gumbs
Jianhua Zhang
Brian Rubin
Anthony Conley
Adrienne M Flanagan
Alexander J Lazar
P Andrew Futreal

Publication Date

10-12-2023

Journal

Human Genetics and Genomic Advances

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

Rhabdomyosarcoma, Sarcoma, TP53, Complex karyotype, Pleomorphic rhabdomyosarcoma

Comments

Supplementary Materials

PMID: 37593416