Loss of Chromosome 3q Is a Prognostic Marker in Fusion-Negative Rhabdomyosarcoma

JCO Precis Oncol. 2023 Sep:7:e2300037. doi: 10.1200/PO.23.00037.

Abstract

Purpose: Soft tissue sarcomas (STS) are rare mesenchymal neoplasms that frequently show complex chromosomal aberrations such as amplifications or deletions of DNA sequences or even whole chromosomes. We recently found that gain of chromosome (chr) 8 is associated with worse overall survival (OS) in STS as a group. We therefore aimed to investigate the overall copy number profile of rhabdomyosarcoma (RMS) to evaluate for prognostic signatures.

Methods: Fluorescence in situ hybridization (FISH) testing was performed on a cohort of STS to assess for chr8 gain. Copy number variation (CNV) data from the National Cancer Institute were analyzed to assess for prognostically significant CNV aberrations in FOXO1 fusion-negative (FN)- versus fusion-positive (FP)-RMS. FISH testing was performed on a cohort of FN-RMS to assess for chr3q loss and correlate with outcomes.

Results: Chr8 gain is a highly prevalent CNV in embryonal RMS and shows slightly improved prognosis. Meanwhile, loss of chr3q was associated with worse outcome in FN-RMS compared with FP-RMS.

Conclusion: The pathogenesis of STS including FN-RMS remains poorly understood, emphasizing the need for new therapeutic advances and adequate risk stratification. Our data demonstrate that loss of chr3q is associated with poor OS in FN-RMS, supporting it as an important tool for risk stratification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes
  • DNA Copy Number Variations*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Prognosis
  • Rhabdomyosarcoma* / diagnosis
  • Rhabdomyosarcoma* / genetics