Ancestral Genetic Homogeneity in Preclinical Models May Shape Outcome Differences in Pediatric Brain Cancer

Area of Science:

• Pediatric neuro-oncology
• Genetics
• Cancer biology

Background:

• Pediatric brain tumors (PBTs) are leading causes of childhood cancer mortality.
• Minority populations experience poorer PBT prognoses, despite efforts to address social determinants and clinical trial access.
• Genetic ancestry may influence PBT biology and treatment response, contributing to outcome disparities.

Purpose of the Study:

• To review the role of genetic ancestry in PBT biology and treatment response.
• To investigate if preclinical models adequately represent ancestral heterogeneity in PBTs.

Main Methods:

• Literature review of studies on genetic ancestry, PBTs, and treatment response.
• Analysis of existing preclinical models for ancestral diversity.

Main Results:

• Population-linked genetic events correlate with tumor biology differences but are under-explored.
• Ancestral variations may affect treatment outcomes, yet few drugs are pharmacogenetically tested across ancestries.
• Brain cancer cell lines lack genetic diversity, predominantly representing European and Asian ancestries.

Conclusions:

• Therapeutic insights are derived from genetically homogeneous populations, limiting clinical translation and exacerbating health disparities.
• Addressing ancestral heterogeneity in PBT research and treatment development is crucial.
• Proposed steps aim to increase ancestral diversity in pediatric neuro-oncology research.