Whole-exome and RNA sequencing reveal novel insights into the pathogenesis of HPV associated cervical cancer

Worldwide, cervical cancer is the fouth leading cause of deaths in gynecological oncology. Although the causes of cervical cancer have been extensively investigated, understanding of its exact pathogenesis remains incomplete.This study aimed to identify alterations of genome and transcriptome of HPV associated cervical cancer pathogenesis using multi-omics approaches.Cervical cancer and matched adjacent non-tumor specimens of one HPV16+ and two HPV- patients were sampled for whole-exome sequencing (WES) and RNA sequencing to characterize DNA mutations and gene expression profiles. WES and Affymetrix SNP 6.0 arrays data were analyzed from 6 HPV- and 93 HPV16+ cervical cancer patients in the cancer genome atlas (TCGA) database, as an independent validation group.WES identified 64 somatic mutation genes in tumors of 3 patients. HPV16+ tumor got fewer somatic mutated genes than HPV- tumors, which was validated by TCGA results. In this study, somatic mutated profile, CNV and gene expression heat map presented that HPV16+ tumors was distinct with HPV- tumors. The most significant altered pathways and GO terms were both related with cell cycle. Integrated analysis of multi-omics showed positive correlation between gene expression level and copy numbers.The results of this study provided novel insights into the pathogenesis of HPV associated cervical cancer.