Abstract
Abstract Recent studies have identified alternative splicing (AS) as a novel source of neoantigens for immunotherapy. Surprisingly little is known about the AS milieu in Pediatric glioma, including diffuse intrinsic pontine glioma (DIPG), pediatric high grade glioma (pHGG) and medulloblastoma. We analyzed 20 primary DIPG, 22 pHGG and 20 medulloblastoma human specimens via RNA sequencing and re-analyzed RNA-sequencing data from non-malignant human brain tissues. From these data, we reconstructed the landscape of AS in Pediatric glioma and contrasted that to observed isoforms in non-malignant brain. We identified novel splicing events in cell-surface proteins that are suitable targets for engineered T-cell therapies in DIPG, pHGG and medulloblastoma. We also identified novel splicing events derived neoantigens in DIPG, pHGG and medulloblastoma respectively, which are potential immunotherapy targets. We found DIPG specific isoforms of Platelet-derived growth factor pathway genes which are expressed exclusively by DIPG tumor cells. Our studies shed light on the effect of immunotherapy on AS and identify novel targets for emerging immunotherapies in pediatric glioma.
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