American Association for Cancer Research
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10780432ccr212484-sup-268834_2_supp_7365585_qyql26.xls (27.5 kB)

Table S4 from Extrachromosomal DNA in HPV-Mediated Oropharyngeal Cancer Drives Diverse Oncogene Transcription

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posted on 2023-03-31, 23:16 authored by John Pang, Nam Nguyen, Jens Luebeck, Laurel Ball, Andrey Finegersh, Shuling Ren, Takuya Nakagawa, Mitchell Flagg, Sayed Sadat, Paul S. Mischel, Guorong Xu, Kathleen Fisch, Theresa Guo, Gabrielle Cahill, Bharat Panuganti, Vineet Bafna, Joseph Califano

Survival analysis of Institutional HPV positive tumors by ecDNA and hybrid classification.

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ARTICLE ABSTRACT

Human papillomavirus (HPV) plays a major role in oncogenesis and circular extrachromosomal DNA (ecDNA) is found in many cancers. However, the relationship between HPV and circular ecDNA in human cancer is not understood. Forty-four primary tumor tissue samples were obtained from a cohort of patients with HPV-positive oropharynx squamous cell carcinoma (OPSCC). Twenty-eight additional HPV oropharyngeal cancer (HPVOPC) tumors from The Cancer Genome Atlas (TCGA) project were analyzed as a separate validation cohort. Genomic, transcriptomic, proteomic, computational, and functional analyses of HPVOPC were applied to these datasets. Our analysis revealed circular, oncogenic DNA in nearly all HPVOPC, with circular human and human–viral hybrid ecDNA present in over a third of HPVOPC and viral circular DNA in remaining tumors. Hybrid ecDNA highly express fusion transcripts from HPV promoters and HPV oncogenes linked to downstream human transcripts that drive oncogenic transformation and immune evasion, and splice multiple, diverse human acceptors to a canonical SA880 viral donor site. HPVOPC have high E6*I expression with specific viral oncogene expression pattern related to viral or hybrid ecDNA composition. Nonchromosomal circular oncogenic DNA is a dominant feature of HPVOPC, revealing an unanticipated link between HPV and ecDNA that leverages the power of extrachromosomal inheritance to drive HPV and somatic oncogene expression.

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