Comprehensive analysis of mutational signatures and corresponding driver genes in cervical cancer from Xinjiang

To investigate the mutational characteristics of cervical cancer in Xinjiang and their relationships with tumor driver genes and affected signaling pathways.

Twenty-nine pairs of cervical cancer tissues and matched peripheral blood samples were subjected to Whole Exome Sequencing. Somatic mutation sites and tumor mutational burden were identified, and core mutational signatures using non-negative matrix factorization (NMF). Driver genes were screened, and pathway enrichment analysis was performed to clarify the associations between core oncogenic pathways and driver genes.

A total of 10,076 nonsynonymous mutations in the coding region were identified. High-frequency mutated genes included members of the MUC family, HRNR, and NBPF1. Single-base substitutions were dominated by C > T (38.63%). Three core mutational signatures were identified: Signature A (undefined), Signature B (APOBEC-mediated deamination), and Signature C (endogenous damage/mismatch repair deficiency). Samples were divided into two groups based on these signatures: Group 1 (high C > G/C > T mutations) and Group 2 (high C > T mutations). Eleven driver genes were identified; among SLC24A1 was a driver gene in both the overall samples and subgroups, suggesting it is a key driver gene in cervical cancer. Gene mutations were mainly enriched in five pathways: NOTCH, RTK-RAS, WNT, Hippo and PI3K. Subgroup pathway signatures consistent with the overall cohort, differing only in mutation frequencies.

This study clarified cervical cancer genomic heterogeneity, revealed core mechanisms (APOBEC activation and endogenous DNA damage), and confirmed SLC24A1 as key driver gene. It provides important genomic evidence for elucidating the pathogenesis of cervical cancer and exploring potential therapeutic targets.