Transposon–gene chimeras move up as cancer epitopes

Transposons are known to sometimes act as alternative promoters for genes, but their reactivation due to epigenetic changes and roles in oncogenesis have remained underexplored. This ectopic expression can give rise to chimeric transcripts and cancer-specific peptides that could be exploited as targets in cancer immunotherapy. A paper in Nature Genetics by Shah et al. reports a bioinformatics workflow called TEProf2 for identifying aberrant transcripts containing transposons spliced into genes. Analysis of over 10,000 tumor samples comprising 33 different cancer types from The Cancer Genome Atlas, together with publicly available mass spectrometry data, led to identification of 1,068 novel chimeric proteins bound to HLA on tumor cell surfaces. Their presentation on the extracellular surface permits exploration of immunotherapy strategies.

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