American Association for Cancer Research
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Supplementary table 1 and figures 1-4 from Endogenous Retrovirus Transcript Levels Are Associated with Immunogenic Signatures in Multiple Metastatic Cancer Types

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journal contribution
posted on 2023-04-03, 18:21 authored by James T. Topham, Emma Titmuss, Erin D. Pleasance, Laura M. Williamson, Joanna M. Karasinska, Luka Culibrk, Michael K.C. Lee, Shehara Mendis, Robert E. Denroche, Gun-Ho Jang, Steve E. Kalloger, Hui-Li Wong, Richard A. Moore, Andrew J. Mungall, Grainne M. O'Kane, Jennifer J. Knox, Steven Gallinger, Jonathan M. Loree, Dixie L. Mager, Janessa Laskin, Marco A. Marra, Steven J.M. Jones, David F. Schaeffer, Daniel J. Renouf

Supplemental Table S1 lists clinical characteristics for the study cohort. Figure S1 depicts results of batch correction. Figures S2 and S3 show comparisons between ERV levels and tumor content. Figure S4 shows ERV levels across different biopsy sites.

Funding

Pancreatic Cancer Canada

Genome British Columbia

Genome Canada and Genome BC

Canada Foundation for Innovation

Canada Research Chairs

CIHR

History

ARTICLE ABSTRACT

Next-generation sequencing of solid tumors has revealed variable signatures of immunogenicity across tumors, but underlying molecular characteristics driving such variation are not fully understood. Although expression of endogenous retrovirus (ERV)-containing transcripts can provide a source of tumor-specific neoantigen in some cancer models, associations between ERV levels and immunogenicity across different types of metastatic cancer are not well established. We performed bioinformatics analysis of genomic, transcriptomic, and clinical data across an integrated cohort of 199 patients with metastatic breast, colorectal, and pancreatic ductal adenocarcinoma tumors. Within each cancer type, we identified a subgroup of viral mimicry tumors in which increased ERV levels were coupled with transcriptional signatures of autonomous antiviral response and immunogenicity. In addition, viral mimicry colorectal and pancreatic tumors showed increased expression of DNA demethylation gene TET2. Taken together, these data demonstrate the existence of an ERV-associated viral mimicry phenotype across three distinct metastatic cancer types, while indicating links between ERV abundance, epigenetic dysregulation, and immunogenicity.