Human papillomavirus integration perspective in small cell cervical carcinoma

• Published in: Nature communications Vol. 13; no. 1; pp. 5968 - 10
• Main Authors: Wang, Xiaoli, Jia, Wenlong, Wang, Mengyao, Liu, Jihong, Zhou, Xianrong, Liang, Zhiqing, Zhang, Qinghua, Long, Sixiang, Quzhen, Suolang, Li, Xiangchun, Tian, Qiang, Li, Xiong, Sun, Haiying, Zhao, Caili, Meng, Silu, Ning, Ruoqi, Xi, Ling, Wang, Lin, Zhou, Shasha, Zhang, Jianwei, Wu, Li, Chen, Yile, Liu, Aijun, Ma, Yaqi, Zhao, Xia, Cheng, Xiaodong, Zhang, Qing, Han, Xiaobing, Pan, Huaxiong, Zhang, Yuan, Cao, Lili, Wang, Yiqin, Ling, Shaoping, Cao, Lihua, Xing, Hui, Xu, Chang, Sui, Long, Wang, Shixuan, Zhou, Jianfeng, Kong, Beihua, Xie, Xing, Chen, Gang, Li, Shuaicheng, Ma, Ding, Li, Shuang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10.10.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13/51; 38/23; 38/39; 38/77; 38/90; 38/91; 45/22; 45/77; 631/67/1858; 692/699/255/2514; 692/699/67/1517/1371; Amplification; Cancer; Cervical cancer; Cervical carcinoma; Cervix; Disease hot spots; Fibroblast growth factor receptors; Gene sequencing; Genes; Genomics; Haplotypes; Human papillomavirus; Humanities and Social Sciences; Integration; Malignancy; multidisciplinary; Myc protein; Next-generation sequencing; Reproduction (copying); Science; Science (multidisciplinary); Transcriptomes; Whole genome sequencing
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-33359-w

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. Small cell cervical carcinoma (SCCC) is a rare but aggressive malignancy. Here, the authors report human papillomavirus features and genomic landscape in SCCC via high-throughput sequencing methods and identify MYC , SOX , NR4A , ANKRD and CEA family genes as HPV-integrated hotspots.