Genomic mutation characteristics and prognosis of biliary tract cancer

The incidence of biliary system cancer is higher in the Chinese population than in the West. The overall prognosis of gallbladder cancer and cholangiocarcinoma is poor, and the current treatment is limited. In order to explore the pathogenesis of biliary tract cancers and potential targeted therapies, we mapped the mutation landscape of biliary tract cancer in the Chinese population and analyzed the molecular mechanism related to prognosis.

A total of 59 formalin fixed paraffin-embedded (FFPE) tissue samples were obtained from patients with operable biliary tract cancer. We conducted targeted capture sequencing of 620 genes through high-throughput sequencing technology and analyzed the fusion information of 13 genes.

Mutations were detected in 88% samples, and the most frequent mutation base was C>T. Genes with higher single nucleotide variations (SNV) and copy number variations (CNV) frequency are TP53, KRAS, ARID1A, VEGFA, cyclin family related genes and cyclin-dependent kinase genes. Actionable mutations were detected in 59.3% samples, and germline mutations were detected in 22% samples. Patients with KRAS mutations, VEGFA pathway mutations and higher tumor mutation burden (TMB) may have poor prognosis.

We explored the mutation characteristics and prognostic mechanism of biliary tract cancers in the Chinese population. This study provides potential evidence for targeted therapy and immunotherapy of biliary tract cancers.