Genetic analysis of Latin American Cervical Cancer

HPV16 is the most oncogenic type of human papillomaviruses (HPV). Integration of HPV into the human genome is an important mechanism of carcinogenesis but is absent in at least 30% of HPV16+ tumors. We applied long-read whole-genome sequencing (WGS) to cervical cancer cell lines and tumors to characterize HPV16 carcinogenesis in the absence of integration. WGS of HPV16+ cervical tumor samples from Latin America revealed that 11/20 tumors with only episomal HPV (EP) had intact monomer episomes. The remaining 9 EP tumors had multimer and rearranged HPV genomes. The majority (80%) of the HPV rearrangements and deletions disrupted the E1 and E2 genes, and EP tumors overexpressed the E6 and E7 viral oncogenes, a similar profile to tumors with HPV integration. Tumors with putative multimer... (for more see dbGaP study page.)

HPV16是致癌性最强的人乳头瘤病毒（human papillomaviruses, HPV）型别。人乳头瘤病毒（HPV）整合进入人类基因组是致癌过程的重要机制之一，但至少30%的HPV16阳性肿瘤中并未发生该整合事件。本研究采用长读长全基因组测序（long-read whole-genome sequencing, WGS）技术，对宫颈癌细胞系及肿瘤样本进行测序，以解析未发生HPV整合情况下的HPV16致癌机制。对来自拉丁美洲的HPV16阳性宫颈肿瘤样本开展全基因组测序后发现，在仅携带游离型HPV（episomal HPV, EP）的20例肿瘤中，有11例存在完整的单体游离病毒基因组；剩余9例游离型HPV肿瘤则携带多聚体及重排后的HPV基因组。HPV基因组的重排与缺失事件中，多数（80%）会破坏E1与E2基因；且游离型HPV肿瘤会过表达病毒致癌基因E6和E7，其分子特征与发生HPV整合的肿瘤相似。携带疑似多聚体基因组的肿瘤……（更多详情请参见dbGaP研究页面）