Age-linked DNA Methylation and Gene Expression in Head and Neck Alveolar Rhabdomyosarcoma

Alveolar rhabdomyosarcoma (ARMS) primarily affects children in the first decade of life, but it can also occur during adolescence, typically with a more favorable prognosis. This study aimed to explore DNA methylation (DNAm) and gene expression differences that could explain the poorer prognosis in younger patients. Whole-genome DNAm and transcriptome analyses were conducted on 10 head and neck ARMS samples, including 4 from patients under 1 year old and 6 from those over 10 years old. Although DNAm profiles were similar across age groups, significant differences in gene expression were identified. These findings suggest potential age-related molecular mechanisms and highlight candidate genes for further investigation as novel therapeutic targets. Notably, CDK9 emerged as a promising target, warranting further exploration in the context of ARMS treatment. Patients were divided in two age groups. Then we performed differential methylation analysis between patients under one year of age (group A) and over 10 years of age (group B), compared the global methylation profile to other reference sarcoma samples (PMID: 33479225) and used them to compute copy number variations (CNVs) and mitotic age (with epiTOC2).