Changes in alternative splicing and associated neo-antigens due to therapy

Recent studies have identified alternative splicing (AS) as a novel source of neoantigens for immunotherapy. Surprisingly little is known about the AS milieu in recurrent glioblastoma (GBM), despite this being the venue for most clinical trials. We profiled 29 primary-recurrent paired human GBM 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 GBM through recurrence and contrasted that to isoforms observed in non-malignant brain. The AS events we identified were cross-referenced with single-cell GBM atlases to determine cell-type specific splicing patterns. From this we identified novel splicing events in cell-surface proteins that are suitable targets for engineered T-cell therapies. We found recurrent-specific isoforms of mitogen-activated kinase pathway genes which are expressed exclusively by GBM stem-like cells that enhance invasiveness. These studies shed light on the effect of therapy on AS and identify novel targets for emerging immunotherapies.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

37 Datasets 1 Publication

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001006744	RNA exome	Illumina NovaSeq 6000	1
EGAD00001006745	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006747	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006748	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006749	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006750	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006751	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006752	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006753	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006754	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006755	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006756	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006757	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006758	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006759	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006760	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006761	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006762	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006763	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006764	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006765	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006766	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006767	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006768	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006769	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006770	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006771	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006772	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006773	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006830	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006831	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006832	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006833	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006834	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006835	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006836	RNA-exome	Illumina NovaSeq 6000	1
EGAD00001006837	RNA-exome	Illumina NovaSeq 6000	1

Publications	Citations
The evolution of alternative splicing in glioblastoma under therapy. Wang L, Shamardani K, Babikir H, Catalan F, Nejo T, Chang S, Phillips JJ, Okada H, Diaz AA. Genome Biol 22: 2021 48	20