Analysis of somatic mutations and key driving factors of cervical cancer progression.

We investigated the somatic mutations and key driving factors of cervical cancer by whole exome sequencing . We found 22,183 somatic single nucleotide variations (SNVs) in 52 paired samples. Somatic SNVs in cervical cancer were significantly higher than those in high-grade intraepithelial lesion and low-grade squamous intraepithelial lesion groups ( < 0.05). C → T/G accounted for 44.12% of base substitution. Copy number variation (false discovery rate < 0.05) was found in 57 chromosome regions. The three regions with significant differences between cervical cancer and non-cervical cancer groups were 1q21.1, 3q26.33, and 13q33.1, covering genes related to tumor proliferation, differentiation, and apoptosis. The frequency of human papillomavirus (HPV) insertion/integration and the number of "" mutations in the cervical cancer group were significantly higher than those in the non-cervical cancer group ( < 0.05). The total number of mutations was positively correlated with the number of "" mutations ( = 0.7967). HPV insertion/integration (OR = 2.302, CI = 1.523-3.589, = 0.0005), enrichment (OR = 17.875, CI = 2.117-150.937, = 0.001), and in (OR = 6.435, CI = 0.823-48.919, = 0.0042) were risk factors for cervical cancer, while in was a protective factor (OR = 0.426, CI = 0.197-0.910, = 0.032). Conclusively, HPV insertion/integration, mutagenesis, and polymorphisms are high-risk factors for cervical cancer and may be causes of genome instability and somatic mutations. This study provides experimental data for revealing the molecular mechanism of cervical cancer.