The Role of "Adult-Onset" Cancer Predisposition Genes in Pediatric Cancer: A Comprehensive Review.
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Current literature estimates that 10% of pediatric cancers are caused by pathogenic or likely pathogenic (P/LP) germline variants in cancer predisposition genes (CPGs). Variants in CPGs thought to increase cancer risk exclusively during adulthood are referred to as "adult-onset" CPGs (aoCPGs). Because next-generation sequencing (NGS)-based molecular tumor profiling, whole genome sequencing (WGS), and whole exome sequencing (WES) are used increasingly in patient assessments, P/LP likely germline aoCPG variants are identified frequently in pediatric patients. However, whether those variants drive cancer development remains an open question. The prevalence of P/LP germline aoCPG variants in pediatric cancers is unclear due to differences in bioinformatics pipelines employed, variability in the aoCPGs analyzed, predominance of small cohort sizes, and a limited number of cancer subtypes analyzed. This review provides a summary of the current literature on aoCPGs in pediatric cancers, identifies gaps in our knowledge, and highlights areas of focus for future research.