The Role of "Adult-Onset" Cancer Predisposition Genes in Pediatric Cancer: A Comprehensive Review

Area of Science:

• Genetics
• Pediatric Oncology
• Genomic Medicine

Background:

• Pathogenic or likely pathogenic (P/LP) germline variants in cancer predisposition genes (CPGs) account for an estimated 10% of pediatric cancers.
• Adult-onset CPGs (aoCPGs) are genes typically associated with cancer risk in adulthood.
• Advances in next-generation sequencing (NGS), whole genome sequencing (WGS), and whole exome sequencing (WES) lead to frequent identification of P/LP germline aoCPG variants in pediatric patients.

Purpose of the Study:

• To review the current literature on aoCPGs in pediatric cancers.
• To identify knowledge gaps regarding the prevalence and impact of P/LP germline aoCPG variants in pediatric cancers.
• To highlight key areas for future research in this field.

Main Methods:

• Literature review of studies reporting aoCPG variants in pediatric cancer patients.
• Analysis of factors contributing to the unclear prevalence of P/LP germline aoCPG variants.
• Synthesis of current evidence and identification of research needs.

Main Results:

• P/LP germline aoCPG variants are identified frequently in pediatric patients due to increased use of comprehensive genomic sequencing.
• The actual prevalence of these variants in pediatric cancers is uncertain.
• Variability in bioinformatics pipelines, aoCPG gene sets, cohort sizes, and cancer subtype analyses contribute to this uncertainty.

Conclusions:

• The clinical significance of P/LP germline aoCPG variants in pediatric cancers remains an open question.
• Further research is needed to accurately determine the prevalence and establish the causality of aoCPGs in pediatric malignancies.
• Standardization of analytical methods and broader analyses across diverse cancer types are crucial for future studies.