Alveolar Rhabdomyosarcoma (ARMS)

Overview

Alveolar Rhabdomyosarcoma is a Soft Tissue Sarcoma subtype of RMS, typically defined by FOXO1 gene fusions.

Cohorts in the corpus

Recurrent alterations

  • FOXO1: fusion partner in 85% of extremity ARMS PMID:37315267.
  • PAX3::FOXO1: present in 70% of ARMS; associated with worse OS and older age than PAX7::FOXO1 (HR 3.45, P=.016) PMID:37315267.
  • PAX7::FOXO1: more favorable prognosis PMID:37315267.
  • MED12, CDK4 amplifications, and CDKN2A deletions: each 8–17% in ARMS; CDK4/CDKN2A events mutually exclusive, enriched in acral/high-risk lesions, correlated with poor OS (P=.02) PMID:37315267.
  • FP-RMS (predominantly ARMS): CDKN2A/CDKN2B deletions 28%, MYCN alterations 22%, CDK4 amplifications 17%; MYCN alterations (p=0.0012) and CDKN2A deletions (p=0.049) each independently predict worse OS; combined alterations show worst OS (p=0.0017) and PFS (p=0.002) PMID:37730754.
  • PAX3::FOXO1 fusion detectable in ctDNA at diagnosis (100%) and relapse (86%), with fusion read counts correlating with disease burden PMID:37730754.
  • Genomic analysis of 147 RMS tumors reclassified ARMS by PAX-fusion status: PAX-fusion-positive (PFP) ARMS carry PAX3- or PAX7-FOXO1 fusions with low somatic mutation burden (mean 6.4 non-synonymous mutations/tumor) and rely on amplifications (MYCN, CDK4, MIR17HG); 7 fusion-negative ARMS clustered molecularly with ERMS PMID:24436047.
  • PIPseq cohort: PAX7-FOXO1 fusion detected by RNA-seq in an alveolar RMS patient despite repeatedly negative FOXO1 break-apart FISH; the fusion was diagnostic and placed the patient in the high-risk prognostic group PMID:28007021

Subtypes

Therapeutic landscape

  • Treated under sequential COG/institutional RMS protocols; CDK4/6-directed strategies not tested but proposed given CDK4-amplified / CDKN2A-deleted subsets PMID:37315267.

Sources

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