Prevalence of CDK4 Amplification in Alveolar Rhabdomyosarcoma Considering Translocation Variants

Abstract

Introduction. Alveolar rhabdomyosarcoma (ARMS) is commonly associated with characteristic fusion transcripts and, in some cases, with oncogene amplifications, including CDK4.

Objective: to determine the prevalence of CDK4 amplification in a cohort of ARMS cases and to evaluate its association with translocation status.

Methods. A retrospective study of 155 formalin-fixed paraffin-embedded tumor samples was performed. CDK4 copy number was assessed by interphase FISH; fusion transcripts were identified by RT-PCR and RNA sequencing. Statistical analysis included calculation of proportions with 95% Clopper-Pearson CIs and χ² tests for comparisons; p<0.05 considered significant.

Results. CDK4 amplification was detected in 22.6% (35/155) of samples. Amplification patterns included low-level (1.5–4 copies), high-level (>4 copies) and clustered signals. Frequencies by translocation subgroup were: PAX3::FOXO1 — 24.7% (25/101), PAX7::FOXO1 — 18.8% (3/16), PAX3::NCOA1 — 25% (1/4), fusion-negative — 17.6% (6/34). No statistically significant associations were found between CDK4 status and clinicopathologic or molecular parameters (p>0.05).

Conclusion. CDK4 amplification is a relatively common genomic event in ARMS; its clinical utility requires further molecular and functional validation.