TP53 germline pathogenic variant frequency in anaplastic rhabdomyosarcoma: A Children’s Oncology Group report

Fair D, Maese L, Chi YY, Li M, Hawkins DS, Venkatramani R, Rudzinski E, Parham D, Teot L, Malkin D, Plon SE, Li H, Sabo A, Lupo PJ, Schiffman JD. TP53 germline pathogenic variant frequency in anaplastic rhabdomyosarcoma: A Children’s Oncology Group report. Pediatr Blood Cancer. 2023 May 17;:e30413. doi: 10.1002/pbc.30413. [Epub ahead of print] PubMed PMID: 37194615; PubMed Central PMCID: PMC10654260.

Rhabdomyosarcoma (RMS) is a well-described cancer in Li-Fraumeni Syndrome (LFS), resulting from germline TP53 pathogenic variants (PVs). RMS exhibiting anaplasia (anRMS) are associated with a high rate of germline TP53 PVs. This study provides updated estimates of the prevalence of TP53 germline PVs in RMS (3%) and anRMS (11%) from a large cohort (n=239) enrolled in five Children’s Oncology Group (COG) clinical trials. Although the prevalence of germline TP53 PVs in patients with anRMS in this series is much lower than previously reported, this prevalence remains elevated. Germline evaluation for TP53 PVs should be strongly considered in patients with anRMS.