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Updated: Aug 5, 2025
10:34
Identification of Sleeping Beauty Transposon Insertions in Solid Tumors using Linker-mediated PCR
Published on: February 1, 2013
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Pan-cancer analysis identifies tumor-specific antigens derived from transposable elements
Nakul M Shah1,2, H Josh Jang1,2,3, Yonghao Liang1,2
1Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
Nature Genetics
|March 27, 2023
Summary
Transposable elements (TEs) reactivated in tumors create novel TE-chimeric antigens (TS-TEAs). These antigens are presented on cancer cell surfaces, offering potential therapeutic targets.
Area of Science:
- Oncology
- Genomics
- Immunology
Background:
- Transposable elements (TEs) are mobile DNA sequences.
- TEs can be reactivated in cancer, leading to novel gene expression.
- This reactivation can generate tumor-specific antigens.
Purpose of the Study:
- To comprehensively screen for TE exaptation events across various cancer types and normal tissues.
- To identify shared tumor-specific TE-chimeric antigens (TS-TEAs).
- To investigate the potential of these TS-TEAs and aberrant membrane proteins as therapeutic targets.
Main Methods:
- Screening of 33 TCGA tumor types, 30 GTEx adult tissues, and 675 cancer cell lines for TE exaptation.
- Identification of TE-exapted candidates using genomic and transcriptomic data.
- Validation using whole-lysate and HLA-pulldown mass spectrometry.
Main Results:
- Identified 1,068 TE-exapted candidates with potential to generate shared TS-TEAs.
- Confirmed presentation of TS-TEAs on the surface of cancer cells via mass spectrometry.
- Highlighted tumor-specific membrane proteins transcribed from TE promoters on cancer cell surfaces.
Conclusions:
- TE exaptation is prevalent across multiple cancer types, generating shared TS-TEAs.
- Aberrant membrane proteins from TE promoters present unique extracellular epitopes.
- These findings suggest potential for novel immunotherapeutic strategies targeting TS-TEAs and aberrant proteins.
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