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Human papillomavirus 42 is an oncogenic driver in Digital Papillary Adenocarcinoma [transductions]

ABSTRACT: The skin serves as a barrier to the environment and is constantly exposed to viral pathogens. However, whether and how viral pathogens contribute to oncogenesis of rare skin cancers has not been explored. We analyzed 18 skin cancers by exploiting sparse off-target reads from commonly available next-generation sequencing data and identify human papillomavirus 42 (HPV42) reads in digital papillary adenocarcinoma (DPA). We show that HPV42 recapitulates the molecular hallmarks of oncogenic HPVs and shares a conserved transcriptomic fingerprint of HPV-transformation. Finally, we show that HPV42 relies on established cellular targets of oncogenic HPVs for its transforming activity. The discovery of HPV42 as a novel oncogenic driver highlights the utility of next-generation sequencing data for the discovery of novel pathogen-disease associations and suggests expansion of current HPV vaccination programs to reduce the cancer burden in humans.

ORGANISM(S): Homo sapiens

PROVIDER: GSE196217 | GEO | 2022/10/10

REPOSITORIES: GEO

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Human papillomavirus 42 is an oncogenic driver in Digital Papillary Adenocarcinoma [full_genomes]

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Quantitative TMT-MS of HPV42, HPV16 or empty vector transduced keratinocytes.

Project description:The skin serves as a barrier to the environment and is constantly exposed to viral pathogens. Whether viral pathogens contribute to the oncogenesis of rare skin cancers has not been systematically explored. Here, we analyzed 18 skin cancer types by exploiting off-target reads from commonly available next-generation sequencing data. We identified human papillomavirus 42 (HPV42) in all digital papillary adenocarcinoma (DPA) cases but not in any of 11,091 tumors from common cancer types. HPV42 was previously not described as an oncogenic driver, yet we show that HPV42 recapitulates the molecular hallmarks of oncogenic HPVs. Using a machine learning approach, we identified a conserved transcriptomic fingerprint of HPV transformation common to oncogenic HPVs, including HPV42. Collectively, our results establish HPV42 as an oncogenic HPV, which has implications for the diagnosis and treatment for DPA patients.

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The Hippo pathway transcription factors YAP and TAZ play HPV-type dependent roles in cervical cancer

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A ubiquitin variant-based affinity approach selectively identifies substrates of the ubiquitin ligase E6AP in complex with HPV-11 E6 or HPV-16 E6

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