Genetic variants found in paediatric oncology patients with severe chemotherapy-induced toxicity: A case series

Area of Science:

• Pharmacogenomics
• Pediatric Oncology
• Genetics

Background:

• Severe chemotherapy-induced toxicity can decrease treatment efficacy in pediatric oncology.
• Established genetic variants (TPMT, NUDT15, UGT1A1, DPYD) inform current pharmacogenetic guidelines.
• Emerging research links novel genetic variants to increased chemotherapy toxicity risk.

Purpose of the Study:

• To investigate the association between novel genetic variants and severe chemotherapy-induced toxicity in pediatric oncology patients.
• To evaluate the potential clinical utility of these novel variants in managing treatment toxicity.

Main Methods:

• Case series design involving nine pediatric oncology patients with excessive chemotherapy-induced toxicity.
• Genotyping of 21 novel genetic variants using whole exome sequencing or microarray data.
• Analysis of identified variants against recent literature linking them to methotrexate or vincristine toxicity.

Main Results:

• Six out of nine patients (67%) carried at least one novel genetic variant associated with increased toxicity risk.
• Identified variants showed potential links to methotrexate- or vincristine-induced toxicity.
• Demonstrated a potential role for these novel variants in explaining observed toxicities.

Conclusions:

• Novel genetic variants may contribute significantly to chemotherapy-induced toxicity in pediatric cancer patients.
• These findings suggest that incorporating novel variant genotyping into clinical practice could help mitigate toxicity.
• Personalized pharmacogenetic approaches using novel variants may improve treatment outcomes and reduce adverse events in pediatric oncology.