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Nat Genet ; 55(4): 631-639, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36973455

RESUMEN

Cryptic promoters within transposable elements (TEs) can be transcriptionally reactivated in tumors to create new TE-chimeric transcripts, which can produce immunogenic antigens. We performed a comprehensive screen for these TE exaptation events in 33 TCGA tumor types, 30 GTEx adult tissues and 675 cancer cell lines, and identified 1,068 TE-exapted candidates with the potential to generate shared tumor-specific TE-chimeric antigens (TS-TEAs). Whole-lysate and HLA-pulldown mass spectrometry data confirmed that TS-TEAs are presented on the surface of cancer cells. In addition, we highlight tumor-specific membrane proteins transcribed from TE promoters that constitute aberrant epitopes on the extracellular surface of cancer cells. Altogether, we showcase the high pan-cancer prevalence of TS-TEAs and atypical membrane proteins that could potentially be therapeutically exploited and targeted.


Asunto(s)
Elementos Transponibles de ADN , Neoplasias , Adulto , Humanos , Elementos Transponibles de ADN/genética , Antígenos de Neoplasias/genética , Regiones Promotoras Genéticas/genética , Neoplasias/genética , Línea Celular
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