Human papillomavirus integration perspective in small cell cervical carcinoma

作者：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

来源：Nature Communications, 2022, 13(1): 5968.

DOI：10.1038/s41467-022-33359-w

• STRUCTURAL VARIATIONS
• HPV INTEGRATION
• CANCER
• GENOME
• PROGRESSION
• METASTASIS
• EXPRESSION
• MUTATIONS

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.

• 单位
  华中科技大学; 1; 山东大学; 上海交通大学; 中山大学; 复旦大学; 四川大学; 西安交通大学