PT  - JOURNAL ARTICLE
AU  - Yu Kong
AU  - Chris Rose
AU  - Ashley A. Cass
AU  - Martine Darwish
AU  - Steve Lianoglou
AU  - Pete M. Haverty
AU  - Ann-Jay Tong
AU  - Craig Blanchette
AU  - Ira Mellman
AU  - Richard Bourgon
AU  - John Greally
AU  - Suchit Jhunjhunwala
AU  - Matthew L. Albert
AU  - Haiyin Chen-Harris
TI  - Transposable Element Exprssion in Tumors is Associated with Immune Infiltration and Increased Antigenicity
AID  - 10.1101/388215
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 388215
4099  - http://biorxiv.org/content/early/2018/08/09/388215.short
4100  - http://biorxiv.org/content/early/2018/08/09/388215.full
AB  - Profound loss of DNA methylation is a well-recognized hallmark of cancer. Given its role in silencing transposable elements (TEs), we hypothesized that extensive TE expression occurs in tumors with highly demethylated DNA. We developed REdiscoverTE, a computational method for quantifying genome-wide TE expression in RNA sequencing data. Using The Cancer Genome Atlas database, we observed increased expression of over 400 TE subfamilies, of which 262 appeared to result from a proximal loss of DNA methylation. The most recurrent TEs were 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 resulted 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 both inflammation and the display of potentially immunogenic neoantigens.One Sentence Summary Transposable element expression in tumors is associated with increased immune response and provides tumor-associated antigens