TY - JOUR T1 - Comprehensive genomic variation profiling of cervical intraepithelial neoplasia and cervical cancer identifies potential targets for cervical cancer early warning JF - Journal of Medical Genetics JO - J Med Genet SP - 186 LP - 194 DO - 10.1136/jmedgenet-2018-105745 VL - 56 IS - 3 AU - Jian Huang AU - Zhaoyang Qian AU - Yuhua Gong AU - Yanzhou Wang AU - Yanfang Guan AU - Yingxin Han AU - Xin Yi AU - Wanqiu Huang AU - Liyan Ji AU - Jiajia Xu AU - Mengyuan Su AU - Qing Yuan AU - Shujian Cui AU - Jinling Zhang AU - Chaohui Bao AU - Weilong Liu AU - Xi Chen AU - Ming Zhang AU - Xiaohuan Gao AU - Renhua Wu AU - Yinxin Zhang AU - Huicheng Xu AU - Shida Zhu AU - Hongmei Zhu AU - Ling Yang AU - Xun Xu AU - Pingyu Zhou AU - Zhiqing Liang Y1 - 2019/03/01 UR - http://jmg.bmj.com/content/56/3/186.abstract N2 - 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. ER -