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 -