Description du projet
Des modifications épigénomiques associées à la progression de l’infection et au cancer
Le papillomavirus humain (HPV) est responsable des maladies sexuellement transmissibles les plus courantes. Bien que les infections initiales par le HPV soient éliminées par le système immunitaire, le HPV persistant peut entraîner un cancer grave de l’oropharynx et du tractus anogénital, qui responsable de 7,5 % des décès annuels par cancer chez les femmes. Les génomes des virus et des hôtes subissent des modifications épigénétiques au cours de l’infection. Le projet METHYVIREVOL, financé par le programme Actions Marie Skłodowska-Curie,entend étudier les liens entre le statut génomique de l’intégration du HPV, les schémas de méthylation dans les cellules cancéreuses et le développement de la maladie. Le projet étudiera en outre les premiers stades de l’infection par le HPV et les modifications de la méthylation de l’ADN viral au cours du développement d’une infection persistante.
Objectif
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.
Champ scientifique
Programme(s)
Régime de financement
MSCA-IF-EF-RI - RI – Reintegration panelCoordinateur
75794 Paris
France