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Virocellular hybrids and epigenomic changes as driving factors of infection driven cancers.

Project description

Epigenomic modifications associated with infection progression and cancer

Human papillomavirus (HPV) causes most common sexually transmitted diseases. Although initial HPV infections are cleared by the immune system, persistent HPV can lead to severe cancer of the oropharynx and anogenital tract, resulting in 7.5% of yearly female cancer deaths. Viral and host genomes undergo epigenetic changes during infection. The Marie Skłodowska-Curie Actions-funded METHYVIREVOL project aims to investigate the links between the genomic status of the HPV integration, the methylation patterns in cancer cells, and disease development. In addition, the project will study the early stages of HPV infection and viral DNA methylation changes during the development of persistent infection.

Objective

Human Papillomavirus (HPV) is the cause of the most common sexually transmitted diseases that the majority of adults will contract during their lifetime. Although most HPV infections are cleared by the immune system within several months, persistent HPV can lead to severe cancers of the oropharynx and anogenital tract. Consequently this DNA virus is a major public health burden accounting for 5% of all cancers worldwide and 7.5% of all female cancer deaths yearly. It is well established that both viral and host genomes undergo significant epigenetic changes during the infectious process. However, the link between the genomic status of the HPV (episomal or integrated), the aberrant methylation patterns of cancer cells and the disease severity remain poorly understood. In addition, the early stages of HPV infection are less studied and viral DNA methylation changes during the progression towards persistent infection is largely unknown. This proposal aims to tackle both problems. In the first workpackage, I will use the publically available data generated by The Cancer Genome Atlas project to study methylation status of the HPV genome focusing in particular on a newly identified HPV-human hybrid episomes. Recently discovered in oropharynx cancer, the biological impact of this form of HPVs on cervical cancer development and the clinical outcome have never been characterized so far. In the second workpackage, I will be using a novel and unique longitudinal clinical study, developed by the host laboratory, following young women infected with HPV. This original data will allow me to decipher DNA methylation changes occurring during the early stage of the HPV infection and their role in disease progression. Together, the data and discoveries generated from this project will answer clinically-relevant questions that will allow the development of new diagnostic approaches of HPV-associated cancers.

Coordinator

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Net EU contribution
€ 173 076,00
Address
RUE MICHEL ANGE 3
75794 Paris
France

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Region
Ile-de-France Ile-de-France Paris
Activity type
Research Organisations
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Total cost
€ 173 076,00