Human papilloma virus integration sites and genomic signatures in head and neck squamous cell carcinoma.
Alphapapillomavirus
Carcinogenesis
Carcinoma, Squamous Cell
/ genetics
DNA
Genomics
Head and Neck Neoplasms
/ genetics
Humans
Kruppel-Like Transcription Factors
Oncogene Proteins, Viral
/ genetics
Papillomaviridae
/ genetics
Papillomavirus Infections
/ complications
Retrospective Studies
Squamous Cell Carcinoma of Head and Neck
/ genetics
MYC
PDL1
HPV copy number
HPV integration
carcinogenesis
head and neck squamous cell carcinoma
Journal
Molecular oncology
ISSN: 1878-0261
Titre abrégé: Mol Oncol
Pays: United States
ID NLM: 101308230
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
revised:
15
02
2022
received:
04
08
2021
accepted:
04
04
2022
pubmed:
11
4
2022
medline:
24
8
2022
entrez:
10
4
2022
Statut:
ppublish
Résumé
A prevalence of around 26% of human papillomavirus (HPV) in head and neck squamous cell carcinoma (HNSCC) has been previously reported. HPV induced oncogenesis mainly involving E6 and E7 viral oncoproteins. In some cases, HPV viral DNA has been detected to integrate with the host genome and possibly contributes to carcinogenesis by affecting the gene expression. We retrospectively assessed HPV integration sites and signatures in 80 HPV positive patients with HNSCC, by using a double capture-HPV method followed by next-generation Sequencing. We detected HPV16 in 90% of the analyzed cohort and confirmed five previously described mechanistic signatures of HPV integration [episomal (EPI), integrated in a truncated form revealing two HPV-chromosomal junctions colinear (2J-COL) or nonlinear (2J-NL), multiple hybrid junctions clustering in a single chromosomal region (MJ-CL) or scattered over different chromosomal regions (MJ-SC) of the human genome]. Our results suggested that HPV remained episomal in 38.8% of the cases or was integrated/mixed in the remaining 61.2% of patients with HNSCC. We showed a lack of association of HPV genomic signatures to tumour and patient characteristics, as well as patient survival. Similar to other HPV associated cancers, low HPV copy number was associated with worse prognosis. We identified 267 HPV-human junctions scattered on most chromosomes. Remarkably, we observed four recurrent integration regions: PDL1/PDL2/PLGRKT (8.2%), MYC/PVT1 (6.1%), MACROD2 (4.1%) and KLF5/KLF12 regions (4.1%). We detected the overexpression of PDL1 and MYC upon integration by gene expression analysis. In conclusion, we identified recurrent targeting of several cancer genes such as PDL1 and MYC upon HPV integration, suggesting a role of altered gene expression by HPV integration during HNSCC carcinogenesis.
Identifiants
pubmed: 35398964
doi: 10.1002/1878-0261.13219
pmc: PMC9394244
doi:
Substances chimiques
KLF12 protein, human
0
Kruppel-Like Transcription Factors
0
Oncogene Proteins, Viral
0
DNA
9007-49-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3001-3016Informations de copyright
© 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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