Human papilloma virus (HPV) integration signature in Cervical Cancer: identification of MACROD2 gene as HPV hot spot integration site
-
Published:2020-11-16
Issue:4
Volume:124
Page:777-785
-
ISSN:0007-0920
-
Container-title:British Journal of Cancer
-
language:en
-
Short-container-title:Br J Cancer
Author:
Kamal Maud, , Lameiras Sonia, Deloger Marc, Morel Adeline, Vacher Sophie, Lecerf Charlotte, Dupain Célia, Jeannot EmmanuelleORCID, Girard Elodie, Baulande Sylvain, Dubot Coraline, Kenter Gemma, Jordanova Ekaterina S.ORCID, Berns Els M. J. J., Bataillon Guillaume, Popovic Marina, Rouzier Roman, Cacheux Wulfran, Le Tourneau ChristopheORCID, Nicolas Alain, Servant Nicolas, Scholl Suzy M., Bièche Ivan
Abstract
Abstract
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.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology
Reference36 articles.
1. Ferlay, J., Soerjomataram, I., Dikshit, R., Eser, S., Mathers, C., Rebelo, M. et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN (2012). Int. J. Cancer 136, E359–E386 (2015). 2. Schiffman, M. H., Bauer, H. M., Hoover, R. N., Glass, A. G., Cadell, D. M., Rush, B. B. et al. Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia. J. Natl Cancer Inst. 85, 958–964 (1993). 3. Wentzensen, N., Vinokurova, S. & von Knebel Doeberitz, M. Systematic review of genomic integration sites of human papillomavirus genomes in epithelial dysplasia and invasive cancer of the female lower genital tract. Cancer Res. 64, 3878–3884 (2004). 4. Crosbie, E. J., Einstein, M. H., Franceschi, S. & Kitchener, H. C. Human papillomavirus and cervical cancer. Lancet 382, 889–899 (2013). 5. Oyervides-Muñoz, M. A., Pérez-Maya, A. A., Rodríguez-Gutiérrez, H. F., Gómez-Macias, G. S., Fajardo-Ramírez, O. R., Treviño, V. et al. Understanding the HPV integration and its progression to cervical cancer. Infect. Genet. Evol. 61, 134–144 (2018).
Cited by
49 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|