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The following is a summary of “Identifying Novel Genetic Markers in Pediatric Rhabdomyosarcoma,” published in the September 2024 issue of Pediatrics by Xu BS et al.

Traditional risk stratification in rhabdomyosarcoma has predominantly relied on histological features and staging. However, emerging evidence underscores the significance of molecular characteristics in prognosis. This study analyzes clinical and genomic data by examining the prognostic impact of age at onset and mutation frequency in rhabdomyosarcoma tumors.

Clinical and genomic data from the Clinomics dataset (n=641) were retrospectively analyzed, focusing on tumors with a minimum mutation incidence of 5% for at least one gene. Patients with unknown risk stratification or age of onset were excluded. Statistical analyses, including ANOVA and Tukey’s HSD, were employed to compare mutation incidence, event-free survival (EFS), and overall survival (OS) across different age groups.

Of the 641 patients, mutations in eight genes—NRAS, BCOR, NF1, TP53, FGFR4, KRAS, HRAS, and CTNNB1—were identified with >5% incidence. The study cohort was comprised of 370 patients divided by age: 51 (0-2 years), 140 (2-5 years), 112 (5-12 years), and 67 (12+ years). A later age of onset correlated with increased incidence of BCOR and HRAS mutations (p<0.005, p<0.001) and was associated with poorer EFS and OS (p<0.05, p<0.001). Specifically, patients with BCOR mutations showed a significant association between later age of onset and poorer EFS and OS (p<0.005, p<0.001). Although NF1 mutations were distributed evenly across age groups (p=0.82), later age of onset was linked to worse EFS and OS (p<0.005, p<0.001).

In patients with rhabdomyosarcoma harboring mutations in BCOR, NF1, TP53, KRAS, HRAS, or CTNNB1, later age of onset is associated with a worse prognosis. This trend is particularly evident in patients with mutations in the tumor suppressors BCOR and NF1. These findings highlight the relevance of integrating age and molecular features into prognostic assessments for more accurate risk stratification and therapeutic strategies.

Source: sciencedirect.com/science/article/pii/S0022346824008327