Human papillomavirus integration perspective in small cell cervical carcinoma

Xiaoli Wang; Wenlong Jia; Mengyao Wang; Jihong Liu; Xianrong Zhou; Zhiqing Liang; Qinghua Zhang; Sixiang Long; Suolang Quzhen; Xiangchun Li; Qiang Tian; Xiong Li; Haiying Sun; Caili Zhao; Silu Meng; Ruoqi Ning; Ling Xi; Lin Wang; Shasha Zhou; Jianwei Zhang; Li Wu; Yile Chen; Aijun Liu; Yaqi Ma; Xia Zhao; Xiaodong Cheng; Qing Zhang; Xiaobing Han; Huaxiong Pan; Yuan Zhang; Lili Cao; Yiqin Wang; Shaoping Ling; Lihua Cao; Hui Xing; Chang Xu; Long Sui; Shixuan Wang; Jianfeng Zhou; Beihua Kong; Xing Xie; Gang Chen; Shuaicheng Li; Ding Ma; Shuang Li

doi:10.1038/s41467-022-33359-w

Human papillomavirus integration perspective in small cell cervical carcinoma

Xiaoli Wang, Wenlong Jia, Mengyao Wang, Jihong Liu, Xianrong Zhou, Zhiqing Liang, Qinghua Zhang, Sixiang Long, Suolang Quzhen, Xiangchun Li, Qiang Tian, Xiong Li, Haiying Sun, Caili Zhao, Silu Meng, Ruoqi Ning, Ling Xi, Lin Wang, Shasha Zhou, Jianwei ZhangLi Wu, Yile Chen, Aijun Liu, Yaqi Ma, Xia Zhao, Xiaodong Cheng, Qing Zhang, Xiaobing Han, Huaxiong Pan, Yuan Zhang, Lili Cao, Yiqin Wang, Shaoping Ling, Lihua Cao, Hui Xing, Chang Xu, Long Sui, Shixuan Wang, Jianfeng Zhou, Beihua Kong, Xing Xie, Gang Chen^*, Shuaicheng Li^*, Ding Ma^*, Shuang Li^*

^*Corresponding author for this work

Shenzhen Research Institute

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

15 Citations (Scopus)

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Abstract

Small cell cervical carcinoma (SCCC) is a rare but aggressive malignancy. Here, we report human papillomavirus features and genomic landscape in SCCC via high-throughput HPV captured sequencing, whole-genome sequencing, whole-transcriptome sequencing, and OncoScan microarrays. HPV18 infections and integrations are commonly detected. Besides MYC family genes (37.9%), we identify SOX (8.4%), NR4A (6.3%), ANKRD (7.4%), and CEA (3.2%) family genes as HPV-integrated hotspots. We construct the genomic local haplotype around HPV-integrated sites, and find tandem duplications and amplified HPV long control regions (LCR). We propose three prominent HPV integration patterns: duplicating oncogenes (MYCN, MYC, and NR4A2), forming fusions (FGFR3–TACC3 and ANKRD12–NDUFV2), and activating genes (MYC) via the cis-regulations of viral LCRs. Moreover, focal CNA amplification peaks harbor canonical cancer genes including the HPV-integrated hotspots within MYC family, SOX2, and others. Our findings may provide potential molecular criteria for the accurate diagnosis and efficacious therapies for this lethal disease.

Original language	English
Article number	5968
Journal	Nature Communications
Volume	13
Issue number	1
Online published	10 Oct 2022
DOIs	https://doi.org/10.1038/s41467-022-33359-w
Publication status	Published - 2022

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This full text is made available under CC-BY 4.0. https://creativecommons.org/licenses/by/4.0/

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@article{c9209cdaa4334f87ba3bfcd21879544c,

title = "Human papillomavirus integration perspective in small cell cervical carcinoma",

abstract = "Small cell cervical carcinoma (SCCC) is a rare but aggressive malignancy. Here, we report human papillomavirus features and genomic landscape in SCCC via high-throughput HPV captured sequencing, whole-genome sequencing, whole-transcriptome sequencing, and OncoScan microarrays. HPV18 infections and integrations are commonly detected. Besides MYC family genes (37.9%), we identify SOX (8.4%), NR4A (6.3%), ANKRD (7.4%), and CEA (3.2%) family genes as HPV-integrated hotspots. We construct the genomic local haplotype around HPV-integrated sites, and find tandem duplications and amplified HPV long control regions (LCR). We propose three prominent HPV integration patterns: duplicating oncogenes (MYCN, MYC, and NR4A2), forming fusions (FGFR3–TACC3 and ANKRD12–NDUFV2), and activating genes (MYC) via the cis-regulations of viral LCRs. Moreover, focal CNA amplification peaks harbor canonical cancer genes including the HPV-integrated hotspots within MYC family, SOX2, and others. Our findings may provide potential molecular criteria for the accurate diagnosis and efficacious therapies for this lethal disease.",

author = "Xiaoli Wang and Wenlong Jia and Mengyao Wang and Jihong Liu and Xianrong Zhou and Zhiqing Liang and Qinghua Zhang and Sixiang Long and Suolang Quzhen and Xiangchun Li and Qiang Tian and Xiong Li and Haiying Sun and Caili Zhao and Silu Meng and Ruoqi Ning and Ling Xi and Lin Wang and Shasha Zhou and Jianwei Zhang and Li Wu and Yile Chen and Aijun Liu and Yaqi Ma and Xia Zhao and Xiaodong Cheng and Qing Zhang and Xiaobing Han and Huaxiong Pan and Yuan Zhang and Lili Cao and Yiqin Wang and Shaoping Ling and Lihua Cao and Hui Xing and Chang Xu and Long Sui and Shixuan Wang and Jianfeng Zhou and Beihua Kong and Xing Xie and Gang Chen and Shuaicheng Li and Ding Ma and Shuang Li",

year = "2022",

doi = "10.1038/s41467-022-33359-w",

language = "English",

volume = "13",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Springer Nature",

number = "1",

}

Wang, X, Jia, W , Wang, M, Liu, J, Zhou, X, Liang, Z, Zhang, Q, Long, S, Quzhen, S, Li, X, Tian, Q, Li, X, Sun, H, Zhao, C, Meng, S, Ning, R, Xi, L, Wang, L, Zhou, S, Zhang, J, Wu, L, Chen, Y, Liu, A, Ma, Y, Zhao, X, Cheng, X, Zhang, Q, Han, X, Pan, H, Zhang, Y, Cao, L, Wang, Y, Ling, S, Cao, L, Xing, H, Xu, C, Sui, L, Wang, S, Zhou, J, Kong, B, Xie, X, Chen, G, Li, S, Ma, D & Li, S 2022, 'Human papillomavirus integration perspective in small cell cervical carcinoma', Nature Communications, vol. 13, no. 1, 5968. https://doi.org/10.1038/s41467-022-33359-w

TY - JOUR

T1 - Human papillomavirus integration perspective in small cell cervical carcinoma

AU - Wang, Xiaoli

AU - Jia, Wenlong

AU - Wang, Mengyao

AU - Liu, Jihong

AU - Zhou, Xianrong

AU - Liang, Zhiqing

AU - Zhang, Qinghua

AU - Long, Sixiang

AU - Quzhen, Suolang

AU - Li, Xiangchun

AU - Tian, Qiang

AU - Li, Xiong

AU - Sun, Haiying

AU - Zhao, Caili

AU - Meng, Silu

AU - Ning, Ruoqi

AU - Xi, Ling

AU - Wang, Lin

AU - Zhou, Shasha

AU - Zhang, Jianwei

AU - Wu, Li

AU - Chen, Yile

AU - Liu, Aijun

AU - Ma, Yaqi

AU - Zhao, Xia

AU - Cheng, Xiaodong

AU - Zhang, Qing

AU - Han, Xiaobing

AU - Pan, Huaxiong

AU - Zhang, Yuan

AU - Cao, Lili

AU - Wang, Yiqin

AU - Ling, Shaoping

AU - Cao, Lihua

AU - Xing, Hui

AU - Xu, Chang

AU - Sui, Long

AU - Wang, Shixuan

AU - Zhou, Jianfeng

AU - Kong, Beihua

AU - Xie, Xing

AU - Chen, Gang

AU - Li, Shuaicheng

AU - Ma, Ding

AU - Li, Shuang

PY - 2022

Y1 - 2022

N2 - Small cell cervical carcinoma (SCCC) is a rare but aggressive malignancy. Here, we report human papillomavirus features and genomic landscape in SCCC via high-throughput HPV captured sequencing, whole-genome sequencing, whole-transcriptome sequencing, and OncoScan microarrays. HPV18 infections and integrations are commonly detected. Besides MYC family genes (37.9%), we identify SOX (8.4%), NR4A (6.3%), ANKRD (7.4%), and CEA (3.2%) family genes as HPV-integrated hotspots. We construct the genomic local haplotype around HPV-integrated sites, and find tandem duplications and amplified HPV long control regions (LCR). We propose three prominent HPV integration patterns: duplicating oncogenes (MYCN, MYC, and NR4A2), forming fusions (FGFR3–TACC3 and ANKRD12–NDUFV2), and activating genes (MYC) via the cis-regulations of viral LCRs. Moreover, focal CNA amplification peaks harbor canonical cancer genes including the HPV-integrated hotspots within MYC family, SOX2, and others. Our findings may provide potential molecular criteria for the accurate diagnosis and efficacious therapies for this lethal disease.

AB - Small cell cervical carcinoma (SCCC) is a rare but aggressive malignancy. Here, we report human papillomavirus features and genomic landscape in SCCC via high-throughput HPV captured sequencing, whole-genome sequencing, whole-transcriptome sequencing, and OncoScan microarrays. HPV18 infections and integrations are commonly detected. Besides MYC family genes (37.9%), we identify SOX (8.4%), NR4A (6.3%), ANKRD (7.4%), and CEA (3.2%) family genes as HPV-integrated hotspots. We construct the genomic local haplotype around HPV-integrated sites, and find tandem duplications and amplified HPV long control regions (LCR). We propose three prominent HPV integration patterns: duplicating oncogenes (MYCN, MYC, and NR4A2), forming fusions (FGFR3–TACC3 and ANKRD12–NDUFV2), and activating genes (MYC) via the cis-regulations of viral LCRs. Moreover, focal CNA amplification peaks harbor canonical cancer genes including the HPV-integrated hotspots within MYC family, SOX2, and others. Our findings may provide potential molecular criteria for the accurate diagnosis and efficacious therapies for this lethal disease.

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UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85139495002&origin=recordpage

U2 - 10.1038/s41467-022-33359-w

DO - 10.1038/s41467-022-33359-w

M3 - RGC 21 - Publication in refereed journal

C2 - 36216793

SN - 2041-1723

VL - 13

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 5968

ER -

Human papillomavirus integration perspective in small cell cervical carcinoma

Abstract

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