Portal de Periódicos da CAPES

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

2020; Springer Nature; Volume: 124; Issue: 4 Linguagem: Inglês

10.1038/s41416-020-01153-4

1532-1827

Maud Kamal, Sonia Lameiras, Marc Deloger, Adeline Morel, Sophie Vacher, Charlotte Lecerf, Célia Dupain, Emmanuelle Jeannot, Elodie Girard, Sylvain Baulande, Coraline Dubot, Gemma G. Kenter, Ekaterina S. Jordanova, Els M.J.J. Berns, Guillaume Bataillon, Marina Popović, Roman Rouzier, Wulfran Cacheux, Christophe Le Tourneau, Alain Nicolas, Nicolas Servant, Suzy Scholl, Ivan Bièche, Anne de la Rochefordière, P. Fumoleau, Aljoša Mandić, Nina Samet, Choumouss Kamoun, Windy Rondoff, Sébastien Armanet, Alexandra Rohel, Souhir Neffati, Marie‐Emmanuelle Legrier, Sinette Ngoumou Mabiala, Sylvain Dureau, Coralie Errera, Marius Craina, Mădălin-Marius Margan, Sanne Samuels, Henry Zijlmans, Peter Hillemanns, Sorin Dema, Alis Dema, Goran Malenković, Branislav Djuran, Anne Floquet, Frédéric Guyon, Pierre Colombo, Michel Fabbro, Christine Kerr, Charlotte Ngô, Fabrice Lécuru, Eleonor Rivin del Campo, Charles Coutant, Frédéric Marchal, Nathalie Mesgouez-Nebout, Virginie Fourchotte, Jean Guillaume Féron, Philippe Morice, Éric Deutsch, Pauline Wimberger, Jean-Marc Classe, Heiko von der Leyen, Mathieu Minsat, I Nagy, Balázs Bálint, Nicolas de Saint-Jorre, Alexia Savignoni, Franck Perez, Patricia Tresca, Noreen Gleeson, Philippe Hupé, Sergio Román-Román, Emmanuel Barillot, Fanny Coffin, Bastiaan Nuijen, Alexandre Boissonnas, Marc Billaud, Laurence Lafanéchère, Jaap Verweij, Arjan Bandel, Jozien Hellemann, Kirsten Ruigrok-Ritstier, Philipp Harter, Christian Kurzeder, Alexander Mustea, Eugéniu Banu, Elisabeta Patcas, Victor Cernat, Andrea Slocker, Michele Mondini, Maud Bossard, Julie Chupin, Sjoerd Rodenhuis, René H. Medema, Anika Havemeier, Thomas Fink, Amelie Michon, Christine Kubiak, Corine M. Beaufort, Judit Cseklye, Dóra Latinovics, Péter Bihari, Isabel Martínez Brito, Bérengère Ouine, Leanne de Koning, Vincent Puard, Elaine Del Nery, Jos H. Beijnen, Dominique Koensgen, Daniela Bruennert, Miloš Lučić, Natalja T. ter Haar,

Colorectal and Anal Carcinomas

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.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.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).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.