Human papilloma virus (HPV) integration signature in Cervical Cancer: identification of MACROD2 gene as HPV hot spot integration site.
Br J Cancer
; 124(4): 777-785, 2021 02.
Article
en En
| MEDLINE
| ID: mdl-33191407
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.
Texto completo:
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Base de datos:
MEDLINE
Asunto principal:
Papillomaviridae
/
Neoplasias del Cuello Uterino
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Integración Viral
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Infecciones por Papillomavirus
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Enzimas Reparadoras del ADN
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Hidrolasas
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
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Risk_factors_studies
Idioma:
En
Revista:
Br J Cancer
Año:
2021
Tipo del documento:
Article