TY - JOUR
T1 - Human papilloma virus (HPV) integration signature in Cervical Cancer
T2 - identification of MACROD2 gene as HPV hot spot integration site
AU - RAIDs Consortium
AU - Kamal, Maud
AU - Lameiras, Sonia
AU - Deloger, Marc
AU - Morel, Adeline
AU - Vacher, Sophie
AU - Lecerf, Charlotte
AU - Dupain, Célia
AU - Jeannot, Emmanuelle
AU - Girard, Elodie
AU - Baulande, Sylvain
AU - Dubot, Coraline
AU - Kenter, Gemma
AU - Jordanova, Ekaterina S.
AU - Berns, Els M.J.J.
AU - Bataillon, Guillaume
AU - Popovic, Marina
AU - Rouzier, Roman
AU - Cacheux, Wulfran
AU - Le Tourneau, Christophe
AU - Nicolas, Alain
AU - Servant, Nicolas
AU - Scholl, Suzy M.
AU - Bièche, Ivan
AU - de la Rochefordiere, Anne
AU - Fumoleau, Pierre
AU - Mandic, Aljosa
AU - Samet, Nina
AU - Kamoun, Choumouss
AU - Rondoff, Windy
AU - Armanet, Sebastien
AU - Rohel, Alexandra
AU - Neffati, Souhir
AU - Legrier, Marie Emmanuelle
AU - Mabiala, Sinette Ngoumou
AU - Dureau, Sylvain
AU - Errera, Coralie
AU - Craina, Marius
AU - Margan, Madalin
AU - Samuels, Sanne
AU - Zijlmans, Henry
AU - Hillemanns, Peter
AU - Dema, Sorin
AU - Dema, Alis
AU - Malenkovic, Goran
AU - Djuran, Branislav
AU - Floquet, Anne
AU - Guyon, Frédéric
AU - Colombo, Pierre Emmanuel
AU - Verweij, Jaap
AU - Beaufort, Corine
N1 - Funding Information:
Funding information This project has received funding from the European Union’s Seventh Program for research, technological development and demonstration under grant agreement no. 304810, the Fondation ARC pour la recherche contre le cancer, the Association d’aide à la recherche en Cancérologie de Saint-Cloud (ARCS), ICGex ANR-10-EQPX-03, and France Génomique ANR-10-INBS-09-08. Funding sources had no involvement in this study and this article.
Publisher Copyright:
© 2020, The Author(s).
PY - 2021/2/16
Y1 - 2021/2/16
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85096001348&partnerID=8YFLogxK
U2 - 10.1038/s41416-020-01153-4
DO - 10.1038/s41416-020-01153-4
M3 - Article
C2 - 33191407
AN - SCOPUS:85096001348
SN - 0007-0920
VL - 124
SP - 777
EP - 785
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 4
ER -
