Human papilloma virus (HPV) integration signature in Cervical Cancer: identification of MACROD2 gene as HPV hot spot integration site

Kamal Maud; Lameiras Sonia; Sameţ Nina; Noi Autori

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KAMAL, Maud, LAMEIRAS, Sonia, SAMEŢ, Nina, NOI, Autori. Human papilloma virus (HPV) integration signature in Cervical Cancer: identification of MACROD2 gene as HPV hot spot integration site. In: British Journal of Cancer, 2021, nr. 4(124), pp. 777-785. ISSN 0007-0920. DOI: https://doi.org/10.1038/s41416-020-01153-4

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British Journal of Cancer

Numărul 4(124) / 2021 / ISSN 0007-0920 /ISSNe 1532-1827

Human papilloma virus (HPV) integration signature in Cervical Cancer: identification of MACROD2 gene as HPV hot spot integration site

DOI:https://doi.org/10.1038/s41416-020-01153-4

Pag. 777-785

Kamal Maud¹², Lameiras Sonia¹², Sameţ Nina³, Noi Autori

¹ Institut Curie,
² PSL Research University, Chimie ParisTech - CNRS, Institut de Recherche de Chimie Paris,
³ Institute of Oncology

Disponibil în IBN: 31 martie 2021

Rezumat

Background: Cervical cancer (CC) remains a leading cause of gynaecological cancer-related mortality with infection by human papilloma virus (HPV) being the most important risk factor. We analysed the association between different viral integration signatures, clinical parameters and outcome in pre-treated CCs. Methods: Different integration signatures were identified using HPV double capture followed by next-generation sequencing (NGS) in 272 CC patients from the BioRAIDs study [NCT02428842]. Correlations between HPV integration signatures and clinical, biological and molecular features were assessed. Results: Episomal HPV was much less frequent in CC as compared to anal carcinoma (p < 0.0001). We identified >300 different HPV-chromosomal junctions (inter- or intra-genic). The most frequent integration site in CC was in MACROD2 gene followed by MIPOL1/TTC6 and TP63. HPV integration signatures were not associated with histological subtype, FIGO staging, treatment or PFS. HPVs were more frequently episomal in PIK3CA mutated tumours (p = 0.023). Viral integration type was dependent on HPV genotype (p < 0.0001); HPV18 and HPV45 being always integrated. High HPV copy number was associated with longer PFS (p = 0.011). Conclusions: This is to our knowledge the first study assessing the prognostic value of HPV integration in a prospectively annotated CC cohort, which detects a hotspot of HPV integration at MACROD2; involved in impaired PARP1 activity and chromosome instability.

Cuvinte-cheie
Human papilloma virus 16, Oropharyngeal Neoplasms, Viral Genes

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