Human papilloma virus (HPV) integration signature in Cervical Cancer: identification of MACROD2 gene as HPV hot spot integration site
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
- Institut Curie
- Antoni van Leeuwenhoek Hospital
- Erasmus University Rotterdam
- Oncology Institute of Vojvodina
- Service d’oncologie médicale
- Publica Institutul Oncologic
- Institut Gustave Roussy
- ARCAGY-GINECO
- Institut Pasteur Paris
- Quanticsoft
- Victor Babes University of Medicine and Pharmacy
- Hannover Medical School (MHH)
- Centre régional de lutte du cancer Val d'Aurelle
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.
Details
Original language | English |
---|---|
Pages (from-to) | 777-785 |
Number of pages | 9 |
Journal | British journal of cancer |
Volume | 124 |
Issue number | 4 |
Publication status | Published - 16 Feb 2021 |
Peer-reviewed | Yes |
External IDs
PubMed | 33191407 |
---|