Shah, Jang, and Liang et al. performed a comprehensive screen of transposable element (TE)-chimeric transcripts across 33 TCGA tumor types with stringent filtering for tumor specificity using comprehensive adult tissue datasets, and demonstrated high pan-cancer prevalence of tumor-specific TE chimeric antigens (TS-TEAs). Whole-lysate and HLA-pulldown mass spectrometry data showed that TS-TEAs were expressed in cancer cells and presented on the surface of cancer cells lines (and tumor samples), respectively. TE promoters also generated truncated or chimeric transcripts of transmembrane proteins on the extracellular surface of cancer cells, which could potentially be therapeutically targeted.
Contributed by Shishir Pant
ABSTRACT: 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.
Author Info: (1) Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA. The Edison Family Center for Genome Sciences and Systems Biology, Washington University Sc
Author Info: (1) Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA. The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA. (2) Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA. The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA. Department of Epigenetics, Van Andel Institute, Grand Rapids, MI, USA. (3) Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA. The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA. (4) Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA. The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA. (5) Donald Danforth Plant Science Center, St. Louis, MO, USA. (6) Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA. The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA. (7) Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA. The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA. (8) Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA. The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA. (9) Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA. The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA. (10) Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA. The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA. (11) Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA. The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA. (12) Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA. The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA. (13) Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA. The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA. (14) Donald Danforth Plant Science Center, St. Louis, MO, USA. (15) Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA. twang@wustl.edu. The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO, USA. twang@wustl.edu. McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA. twang@wustl.edu.
