Pediatric Oncology Patients With Germline Pathogenic Variants in Adult-Onset Cancer Predisposition Genes

Area of Science:

• Pediatric Oncology
• Cancer Genetics
• Germline Pathogenic Variants

Background:

• Adult-onset cancer predisposition genes (aoCPG) typically have low cancer risk in children.
• Germline pathogenic variants (GPV) in aoCPG are usually identified in adults.
• The role of GPV in aoCPG in pediatric cancer is often unclear.

Purpose of the Study:

• To investigate the role of GPV in aoCPG in the development of childhood cancer.
• To determine the frequency of GPV in aoCPG among pediatric oncology patients.
• To assess the potential contribution of aoCPG to pediatric cancer diagnoses.

Main Methods:

• Analysis of paired tumor-germline sequencing data from 954 pediatric oncology patients.
• Germline testing included up to 182 cancer predisposition genes.
• Tumor findings like loss-of-heterozygosity and somatic variants were used to infer causation.

Main Results:

• 4.4% of pediatric oncology patients (42/954) had GPV in aoCPG.
• In 14.3% of these cases (6/42), tumor findings suggested the GPV likely contributed to cancer.
• Identified cases included Lynch syndrome, and GPV in ATM, BRIP1, and CHEK2 associated with various pediatric tumors.

Conclusions:

• GPV in aoCPG can rarely contribute to childhood cancer diagnoses.
• This finding challenges the traditional classification of these genes as solely adult-onset.
• Further research may refine genetic testing and screening protocols for pediatric cancer risk.