TY - JOUR
T1 - Human papilloma virus integration sites and genomic signatures in head and neck squamous cell carcinoma
AU - Mainguené, Juliette
AU - Vacher, Sophie
AU - Kamal, Maud
AU - Hamza, Abderaouf
AU - Masliah-Planchon, Julien
AU - Baulande, Sylvain
AU - Ibadioune, Sabrina
AU - Borcoman, Edith
AU - Cacheux, Wulfran
AU - Calugaru, Valentin
AU - Courtois, Laura
AU - Crozes, Carole
AU - Deloger, Marc
AU - Girard, Elodie
AU - Delord, Jean Pierre
AU - Dubray-Vautrin, Antoine
AU - Larbi Chérif, Linda
AU - Dupain, Celia
AU - Jeannot, Emmanuelle
AU - Klijanienko, Jerzy
AU - Lameiras, Sonia
AU - Lecerf, Charlotte
AU - Modesto, Anouchka
AU - Nicolas, Alain
AU - Rouzier, Roman
AU - Saada-Bouzid, Esma
AU - Saintigny, Pierre
AU - Sudaka, Anne
AU - Servant, Nicolas
AU - Le Tourneau, Christophe
AU - Bièche, Ivan
N1 - Publisher Copyright:
© 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
PY - 2022/8/1
Y1 - 2022/8/1
N2 - 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.
AB - 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.
KW - HPV copy number
KW - HPV integration
KW - MYC
KW - PDL1
KW - carcinogenesis
KW - head and neck squamous cell carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85129752930&partnerID=8YFLogxK
U2 - 10.1002/1878-0261.13219
DO - 10.1002/1878-0261.13219
M3 - Article
C2 - 35398964
AN - SCOPUS:85129752930
SN - 1574-7891
VL - 16
SP - 3001
EP - 3016
JO - Molecular Oncology
JF - Molecular Oncology
IS - 16
ER -