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Human papillomavirus integration perspective in small cell cervical carcinoma

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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 [3]City Univ Hong Kong, Shenzhen Res Inst, Shenzhen, Peoples R China [4]Sun Yat Sen Univ, Dept Gynecol Oncol, Canc Ctr, State Key Lab Oncol South China,Collaborat Innova, Guangzhou, Peoples R China [5]Fudan Univ, Obstetr & Gynecol Hosp, Shanghai, Peoples R China [6]Third Mil Med Univ, Southwest Hosp, Dept Gynecol Oncol, Chongqing, Peoples R China [7]Cent Hosp Wuhan, Dept Gynecol & Obstet, Wuhan, Peoples R China [8]Tianjin Med Univ, Tianjin Canc Inst, Natl Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy,Canc Inst & Hosp, Tianjin, Peoples R China [9]Shanghai Jiao Tong Univ, Natl Infrastruct Translat Med Shanghai, Sch Med, Shanghai, Peoples R China [10]Hunan ProvinceTumor Hosp, Dept Gynecol Oncol, Changsha, Peoples R China [11]Chinese Peoples Liberat Army Gen Hosp, Dept Pathol, Beijing, Peoples R China [12]Sichuan Univ, West China Hosp 2, Dept Gynecol Oncol, Chengdu, Sichuan, Peoples R China [13]Womens Reprod Hlth Lab Zhejiang Prov, Hangzhou, Zhejiang, Peoples R China [14]Shandong Univ, Qilu Hosp, Dept Gynecol & Obstet, Jinan, Shandong, Peoples R China [15]Xi An Jiao Tong Univ, Gynecol, Affiliated Hosp 1, Med Sch, Xian, Peoples R China [16]Huazhong Univ Sci & Technol, UnionHosp, Tongji Med Coll, Beijing, Peoples R China [17]Genome Wisdom Inc, Beijing, Peoples R China [18]Huazhong Univ Sci & Technol, Tongji Med Coll, Xiangfan Cent Hosp, Dept Obstet & Gynecol, Xiangfan, Hubei, Peoples R China
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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.

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大类 | 1 区 综合性期刊
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Q1 MULTIDISCIPLINARY SCIENCES
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Q1 MULTIDISCIPLINARY SCIENCES

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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
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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
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