The neoepitope landscape in pediatric cancers

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Neoepitopes from tumor mutations are key for childhood cancer immunotherapy.
• Knowledge of the pediatric cancer neoepitope landscape is limited.
• Previous studies overlooked gene fusions, crucial oncogenic drivers in pediatric cancers.

Purpose of the Study:

• To develop a workflow for identifying neoepitopes from somatic mutations and gene fusions.
• To analyze the neoepitope landscape in childhood cancer genomes and transcriptomes.
• To facilitate the development of novel immunotherapies for pediatric cancers.

Main Methods:

• Developed an analytical workflow for neoepitope identification.
• Utilized whole-genome and transcriptome sequencing data.
• Incorporated analysis of somatic missense mutations and gene fusions.

Main Results:

• Mapped the neoepitope landscape across 540 childhood cancer genomes/transcriptomes (23 subtypes).
• Found that 88% of leukemias, 78% of CNS tumors, and 90% of solid tumors possess predicted neoepitopes.
• Identified potential epitopes from KRAS, histone H3 mutations, and the ETV6-RUNX1 fusion.

Conclusions:

• Presents a comprehensive repertoire of potential neoepitopes in childhood cancers.
• Provides a foundation for developing targeted immunotherapeutic strategies.
• Workflow code is publicly available on GitHub.