Pan-cancer Analysis Identifies Tumor-specific Antigens Derived from Transposable Elements

Overview

Journal Nat Genet

Specialty Genetics

Date 2023 Mar 27

PMID 36973455

Authors

Nakul M Shah

H Josh Jang

Yonghao Liang

Ju Heon Maeng

Shin-Cheng Tzeng

Angela Wu

Noah L Basri

Xuan Qu

Changxu Fan

Amy Li

Benjamin Katz

Daofeng Li

Xiaoyun Xing

Bradley S Evans

Ting Wang

Affiliations

Soon will be listed here.

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.

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