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.
基金:
Major Research Plan of the National Natural Science Foundation of China [91529102]; National Natural Science Foundation of China [81974410, 81572571, 81630060, 81230038, 81472783, 81272422, 81472444, 81402160, 81302267]; Key Basic Research and Development Program Foundation of China (973 Program) [2015CB553903]; National Science-technology Supporting Projects [2015BAI13B05]; Chinese national key plan of precision medicine research [2016YFC0902900]; Special Funding on Rare Tumors [82141106]
第一作者机构:[1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Obstet & Gynecol, Wuhan, Peoples R China[2]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Canc Biol Res Ctr, 1095 Jiefang Ave, Wuhan 430030, Hubei, Peoples R China
共同第一作者:
通讯作者:
通讯机构:[1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Obstet & Gynecol, Wuhan, Peoples R China[2]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Canc Biol Res Ctr, 1095 Jiefang Ave, Wuhan 430030, Hubei, Peoples R China
推荐引用方式(GB/T 7714):
Wang Xiaoli,Jia Wenlong,Wang Mengyao,et al.Human papillomavirus integration perspective in small cell cervical carcinoma[J].NATURE COMMUNICATIONS.2022,13(1):doi:10.1038/s41467-022-33359-w.
APA:
Wang, Xiaoli,Jia, Wenlong,Wang, Mengyao,Liu, Jihong,Zhou, Xianrong...&Li, Shuang.(2022).Human papillomavirus integration perspective in small cell cervical carcinoma.NATURE COMMUNICATIONS,13,(1)
MLA:
Wang, Xiaoli,et al."Human papillomavirus integration perspective in small cell cervical carcinoma".NATURE COMMUNICATIONS 13..1(2022)