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Multi-omics characterization of silent and productive HPV integration in cervical cancer

Cervical cancer (CC) that is caused by high-risk human papillomavirus (HPV) remains a significant public health problem worldwide. HPV integration sites can be silent or actively transcribed, leading to the production of viral-host fusion transcripts. Herein, we demonstrate that only productive HPV...

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Autores principales: Fan, Junpeng, Fu, Yu, Peng, Wenju, Li, Xiong, Shen, Yuanming, Guo, Ensong, Lu, Funian, Zhou, Shengtao, Liu, Si, Yang, Bin, Qin, Xu, Hu, Dianxing, Xiao, Rourou, Li, Xi, Yang, Siqi, Yuan, Cunzhong, Shu, Yao, Huang, He, Wan, Ting, Pi, Yanan, Wang, Shuxiang, Chen, Wenjuan, Wang, Haixia, Zhong, Lin, Yuan, Li, Wen, Baogang, Kong, Beihua, Mills, Gordon B., Zou, Dongling, Xia, Bairong, Song, Kun, Chen, Gang, Ma, Ding, Sun, Chaoyang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9903858/
https://www.ncbi.nlm.nih.gov/pubmed/36777180
http://dx.doi.org/10.1016/j.xgen.2022.100211
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author Fan, Junpeng
Fu, Yu
Peng, Wenju
Li, Xiong
Shen, Yuanming
Guo, Ensong
Lu, Funian
Zhou, Shengtao
Liu, Si
Yang, Bin
Qin, Xu
Hu, Dianxing
Xiao, Rourou
Li, Xi
Yang, Siqi
Yuan, Cunzhong
Shu, Yao
Huang, He
Wan, Ting
Pi, Yanan
Wang, Shuxiang
Chen, Wenjuan
Wang, Haixia
Zhong, Lin
Yuan, Li
Wen, Baogang
Kong, Beihua
Mills, Gordon B.
Zou, Dongling
Xia, Bairong
Song, Kun
Chen, Gang
Ma, Ding
Sun, Chaoyang
author_facet Fan, Junpeng
Fu, Yu
Peng, Wenju
Li, Xiong
Shen, Yuanming
Guo, Ensong
Lu, Funian
Zhou, Shengtao
Liu, Si
Yang, Bin
Qin, Xu
Hu, Dianxing
Xiao, Rourou
Li, Xi
Yang, Siqi
Yuan, Cunzhong
Shu, Yao
Huang, He
Wan, Ting
Pi, Yanan
Wang, Shuxiang
Chen, Wenjuan
Wang, Haixia
Zhong, Lin
Yuan, Li
Wen, Baogang
Kong, Beihua
Mills, Gordon B.
Zou, Dongling
Xia, Bairong
Song, Kun
Chen, Gang
Ma, Ding
Sun, Chaoyang
author_sort Fan, Junpeng
collection PubMed
description Cervical cancer (CC) that is caused by high-risk human papillomavirus (HPV) remains a significant public health problem worldwide. HPV integration sites can be silent or actively transcribed, leading to the production of viral-host fusion transcripts. Herein, we demonstrate that only productive HPV integration sites were nonrandomly distributed across both viral and host genomes, suggesting that productive integration sites are under selection and likely to contribute to CC pathophysiology. Furthermore, using large-scale, multi-omics (clinical, genomic, transcriptional, proteomic, phosphoproteomic, and single-cell) data, we demonstrate that tumors with productive HPV integration are associated with higher E6/E7 proteins and enhanced tumor aggressiveness and immunoevasion. Importantly, productive HPV integration increases from carcinoma in situ to advanced disease. This study improves our understanding of the functional consequences of HPV fusion transcripts on the biology and pathophysiology of HPV-driven CCs, suggesting that productive HPV integration should be evaluated as an indicator of high risk for progression to aggressive cancers.
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spelling pubmed-99038582023-02-10 Multi-omics characterization of silent and productive HPV integration in cervical cancer Fan, Junpeng Fu, Yu Peng, Wenju Li, Xiong Shen, Yuanming Guo, Ensong Lu, Funian Zhou, Shengtao Liu, Si Yang, Bin Qin, Xu Hu, Dianxing Xiao, Rourou Li, Xi Yang, Siqi Yuan, Cunzhong Shu, Yao Huang, He Wan, Ting Pi, Yanan Wang, Shuxiang Chen, Wenjuan Wang, Haixia Zhong, Lin Yuan, Li Wen, Baogang Kong, Beihua Mills, Gordon B. Zou, Dongling Xia, Bairong Song, Kun Chen, Gang Ma, Ding Sun, Chaoyang Cell Genom Article Cervical cancer (CC) that is caused by high-risk human papillomavirus (HPV) remains a significant public health problem worldwide. HPV integration sites can be silent or actively transcribed, leading to the production of viral-host fusion transcripts. Herein, we demonstrate that only productive HPV integration sites were nonrandomly distributed across both viral and host genomes, suggesting that productive integration sites are under selection and likely to contribute to CC pathophysiology. Furthermore, using large-scale, multi-omics (clinical, genomic, transcriptional, proteomic, phosphoproteomic, and single-cell) data, we demonstrate that tumors with productive HPV integration are associated with higher E6/E7 proteins and enhanced tumor aggressiveness and immunoevasion. Importantly, productive HPV integration increases from carcinoma in situ to advanced disease. This study improves our understanding of the functional consequences of HPV fusion transcripts on the biology and pathophysiology of HPV-driven CCs, suggesting that productive HPV integration should be evaluated as an indicator of high risk for progression to aggressive cancers. Elsevier 2023-01-11 /pmc/articles/PMC9903858/ /pubmed/36777180 http://dx.doi.org/10.1016/j.xgen.2022.100211 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Fan, Junpeng
Fu, Yu
Peng, Wenju
Li, Xiong
Shen, Yuanming
Guo, Ensong
Lu, Funian
Zhou, Shengtao
Liu, Si
Yang, Bin
Qin, Xu
Hu, Dianxing
Xiao, Rourou
Li, Xi
Yang, Siqi
Yuan, Cunzhong
Shu, Yao
Huang, He
Wan, Ting
Pi, Yanan
Wang, Shuxiang
Chen, Wenjuan
Wang, Haixia
Zhong, Lin
Yuan, Li
Wen, Baogang
Kong, Beihua
Mills, Gordon B.
Zou, Dongling
Xia, Bairong
Song, Kun
Chen, Gang
Ma, Ding
Sun, Chaoyang
Multi-omics characterization of silent and productive HPV integration in cervical cancer
title Multi-omics characterization of silent and productive HPV integration in cervical cancer
title_full Multi-omics characterization of silent and productive HPV integration in cervical cancer
title_fullStr Multi-omics characterization of silent and productive HPV integration in cervical cancer
title_full_unstemmed Multi-omics characterization of silent and productive HPV integration in cervical cancer
title_short Multi-omics characterization of silent and productive HPV integration in cervical cancer
title_sort multi-omics characterization of silent and productive hpv integration in cervical cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9903858/
https://www.ncbi.nlm.nih.gov/pubmed/36777180
http://dx.doi.org/10.1016/j.xgen.2022.100211
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