Whole-genome Sequencing Analysis of Bile Tract Cancer Reveals Mutation Characteristics and Potential Biomarkers

Background/aim: Bile tract cancer (BTC) is a malignant tumor with a poor prognosis. Recent studies have reported the heterogeneity of the genomic background and gene alterations in BTC, but its genetic heterogeneity and molecular profiles remain poorly understood. Whole-genome sequencing may enable the identification of novel actionable gene mutations involved in BTC carcinogenesis, malignant progression, and treatment resistance.

Patients and methods: We performed whole-genome sequencing of six BTC samples to elucidate its genetic heterogeneity and identify novel actionable gene mutations. Somatic mutations, structural variations, copy number alterations, and their associations with clinical factors were analyzed.

Results: The average number of somatic mutations detected in each case was 53,705, with SNVs accounting for most of these mutations (85.02%). None of the 331 mutations related to BTC in The Cancer Genome Atlas (TCGA) database were found in the mutations identified in our study. A higher prevalence of gene mutations was observed in samples without vascular invasion than in those with vascular invasion. Several genes with differences in mutation accumulation between groups were identified, including ADAMTS7, AHNAK2, and CAPN10.

Conclusion: Our study provides novel insights into the genomic landscape of BTC and highlights the potential of whole-genome sequencing analysis to identify actionable gene mutations and understand the molecular mechanisms underlying this malignancy. The high mutational burden, structural variations, and copy number alterations observed in BTC samples in this study underscore the genetic complexity and heterogeneity of this disease.