To analyze transposable element (TE) expression in the genome, Kong et al. produced a computational method REdiscoverTE. In TCGA and Cancer Genome Project data sets, various TE subfamilies, particularly from evolutionarily young TEs, were overexpressed in tumor tissue based on the cancer type. TE expression correlated with proximal DNA demethylation and expression of immune and DNA damage response genes. In glioblastoma cell lines, reversing DNA methylation with decitabine increased expression of TEs and TE-derived peptides detected in the proteome and MHC peptidome for potential recognition by antitumor T cells.
Contributed by Alex Najibi
Profound global loss of DNA methylation is a hallmark of many cancers. One potential consequence of this is the reactivation of transposable elements (TEs) which could stimulate the immune system via cell-intrinsic antiviral responses. Here, we develop REdiscoverTE, a computational method for quantifying genome-wide TE expression in RNA sequencing data. Using The Cancer Genome Atlas database, we observe increased expression of over 400 TE subfamilies, of which 262 appear to result from a proximal loss of DNA methylation. The most recurrent TEs are among the evolutionarily youngest in the genome, predominantly expressed from intergenic loci, and associated with antiviral or DNA damage responses. Treatment of glioblastoma cells with a demethylation agent results in both increased TE expression and de novo presentation of TE-derived peptides on MHC class I molecules. Therapeutic reactivation of tumor-specific TEs may synergize with immunotherapy by inducing inflammation and the display of potentially immunogenic neoantigens.
Author Info: (1) Department of Genetics and Center for Epigenomics, Albert Einstein College of Medicine, New York, 10461, USA. (2) Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, US
Author Info: (1) Department of Genetics and Center for Epigenomics, Albert Einstein College of Medicine, New York, 10461, USA. (2) Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA. (3) Department of Bioinformatics Interdepartmental Program, University of California at Los Angeles, Los Angeles, CA, USA. (4) Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA. (5) Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA. (6) Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA. (7) Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA. (8) Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA. (9) Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA. (10) Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA. (11) Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA. (12) Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA. (13) Department of Genetics and Center for Epigenomics, Albert Einstein College of Medicine, New York, 10461, USA. (14) Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA. (15) Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA. haiyin@argonautgenomics.com. Argonaut Genomics, Inc., 1025 Alameda De Las Pulgas #806, Belmont, CA, 94002, USA. haiyin@argonautgenomics.com.
