Hypothesis-generating analysis of mutational signatures in childhood B-cell acute lymphoblastic leukemia in relation to socio-demographic, genetic, and environmental factors: A report from the Children’s Oncology Group

Clark CJ, Lu Z, Anderson N, Li Y, Park JE, Love M, Marcotte E, de Smith AJ, Spector LG. Hypothesis-generating analysis of mutational signatures in childhood B-cell acute lymphoblastic leukemia in relation to socio-demographic, genetic, and environmental factors: A report from the Children’s Oncology Group. medRxiv [Preprint]. 2025 Oct 9:2025.10.02.25336752. doi: 10.1101/2025.10.02.25336752. PMID: 41282801; PMCID: PMC12632680.

Signatures of mutational processes (mutSig) have the potential to fingerprint exposures present during tumor development. While several studies have described prevalence and burden of mutSig in pediatric populations, there have been few efforts to date to associate mutational signatures with exposures or lifestyle factors related to cancer risk. Studying relationships between mutSig and pediatric cancer risk factors can inform future etiologic studies and elucidate the critical exposure pathways underlying cancer risk.