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Germline Variants in Pediatric Cancer : Based on Oncogenic Pathways
Joo Whan Kim1,2
1Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Korea.
Journal of Korean Neurosurgical Society
|February 17, 2025
Summary
Pathogenic germline variants (PGVs) are key in pediatric cancer. Understanding these genetic changes, often inherited, aids in early detection and personalized treatment for childhood cancers.
Area of Science:
- Genomic Medicine
- Pediatric Oncology
- Cancer Genomics
Background:
- Pathogenic germline variants (PGVs) are increasingly recognized in pediatric cancer predisposition.
- Next-generation sequencing and genome databases are advancing the understanding of cancer genomics.
- PGVs play roles in key oncogenic pathways like RTK/RAS/MAPK, PI3K/AKT, WNT, and Hedgehog signaling.
Purpose of the Study:
- To review the role of PGVs in pediatric cancer predisposition syndromes.
- To highlight neurosurgical implications of PGVs.
- To emphasize the importance of germline screening and genomic databases for personalized medicine.
Main Methods:
- Review of existing literature on PGVs in pediatric cancer.
- Analysis of PGVs in specific oncogenic pathways and associated syndromes.
- Discussion of the prevalence and inheritance patterns of PGVs.
Main Results:
- PGVs are associated with various cancer predisposition syndromes, often inherited dominantly.
- RASopathies and syndromes like Cowden and DICER1 are linked to specific PGVs.
- Approximately 8.5-20% of pediatric cancer patients harbor PGVs, with many arising de novo.
Conclusions:
- Routine germline screening for pediatric cancer patients is recommended due to de novo occurrences and lack of family history.
- Comprehensive pediatric genome databases are crucial for personalized precision medicine.
- International collaboration is needed to advance pediatric cancer genomics for improved diagnostics, therapeutics, and prevention.
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