Comprehensive genomic variation profiling of cervical intraepithelial neoplasia and cervical cancer identifies potential targets for cervical cancer early warning. Issue 3 (19th December 2018)

• Record Type: Journal Article
• Authors: Huang, Jian; Qian, Zhaoyang; Gong, Yuhua; Wang, Yanzhou; Guan, Yanfang; Han, Yingxin; Yi, Xin; Huang, Wanqiu; Ji, Liyan; Xu, Jiajia; Su, Mengyuan; Yuan, Qing; Cui, Shujian; Zhang, Jinling; Bao, Chaohui; Liu, Weilong; Chen, Xi; Zhang, Ming; Gao, Xiaohuan; Wu, Renhua; Zhang, Yinxin; Xu, Huicheng; Zhu, Shida; Zhu, Hongmei; Yang, Ling; Xu, Xun; Zhou, Pingyu; Liang, Zhiqing
• Is Part Of: Journal of medical genetics. Volume 56:Issue 3(2019)
• Page Start: 186
• Page End: 194
• Publication Date: 2018-12-19
• Subjects: cervical cancer -- pathogenesis -- genomic variation -- human papillomavirus integration; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmedgenet-2018-105745
• Languages: English
• ISSNs: 1468-6244

Abstract

Abstract : Background: To better understand the pathogenesis of cervical cancer (CC), we systematically analysed the genomic variation and human papillomavirus (HPV) integration profiles of cervical intraepithelial neoplasia (CIN) and CC. Methods: We performed whole-genome sequencing or whole-exome sequencing of 102 tumour-normal pairs and human papillomavirus probe capture sequencing of 45 CCs, 44 CIN samples and 25 normal cervical samples, and constructed strict integrated workflow of genomic analysis. Results: Mutational analysis identified eight significantly mutated genes in CC including four genes ( FAT1, MLL3, MLL2 and FADD ), which have not previously been reported in CC. Targetable alterations were identified in 55.9% of patients. In addition, HPV integration breakpoints occurred in 97.8% of the CC samples, 70.5% of the CIN samples and 42.8% of the normal cervical samples with HPV infection. Integrations of high-risk HPV strains in CCs, including HPV16, 18, 33 and 58, also occurred in the CIN samples. Moreover, gene mutations were detected in 52% of the CIN specimens, and 54.8% of these mutations occurred in genes that also mutated in CCs. Conclusion: Our results lay the foundation for a deep understanding of the molecular mechanisms and finding new diagnostic and therapeutic targets of CC.