Identification of whole-genome mutations and structural variations of bile cell-free DNA in cholangiocarcinoma

Bile cell-free DNA (cfDNA) has been reported as a promising liquid biopsy tool for cholangiocarcinoma (CCA), however, the whole-genome mutation landscape and structural variants (SVs) of bile cfDNA remains unknown. Here we performed whole-genome sequencing on bile cfDNA and analyzed the correlation between mutation characteristics of bile cfDNA and clinical prognosis. TP53 and KRAS were the most frequently mutated genes, and the RTK/RAS, homologous recombination (HR), and HIPPO were top three pathways containing most gene mutations. Ten overlapping putative driver genes were found in bile cfDNA and tumor tissue. SVs such as chromothripsis and kataegis were identified. Moreover, the hazard ratio of HR pathway mutations were 15.77 (95% CI: 1.571-158.4), patients with HR pathway mutations in bile cfDNA exhibited poorer overall survival (P = 0.0049). Our study suggests that bile cfDNA contains genome mutations and SVs, and HR pathway mutations in bile cfDNA can predict poor outcomes of CCA patients.

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Publication Details

Journal
Genomics
Published
2024-08-13
DOI
https://doi.org/10.1016/j.ygeno.2024.110916
Citations
5
Primary Topic
Cholangiocarcinoma and Gallbladder Cancer Studies
Type
article
Field-Weighted Citation Impact
2.86
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article

Identification of whole-genome mutations and structural variations of bile cell-free DNA in cholangiocarcinoma

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5 citations
Genomics
Cholangiocarcinoma and Gallbladder Cancer Studies
2.86
article

Identification of whole-genome mutations and structural variations of bile cell-free DNA in cholangiocarcinoma

Dadong Zhang, Qiaonan Duan, Yan–Xin Chang, Teng Zhao, Dongyu Liu, Longjiu Cui, Zhikuan Li, Baoning Nian, Hao Chen, Bin Li, Xiang Wang, Yongjie Zhang, Jian Liu, Wei Zhang, Xiaoya Xu, Sheng Chen, Lei Yin, Lixue Yang, Anqi Duan, Y. P. Kuang, Kai Lu
article en
5 citations

Abstract

Bile cell-free DNA (cfDNA) has been reported as a promising liquid biopsy tool for cholangiocarcinoma (CCA), however, the whole-genome mutation landscape and structural variants (SVs) of bile cfDNA remains unknown. Here we performed whole-genome sequencing on bile cfDNA and analyzed the correlation between mutation characteristics of bile cfDNA and clinical prognosis. TP53 and KRAS were the most frequently mutated genes, and the RTK/RAS, homologous recombination (HR), and HIPPO were top three pathways containing most gene mutations. Ten overlapping putative driver genes were found in bile cfDNA and tumor tissue. SVs such as chromothripsis and kataegis were identified. Moreover, the hazard ratio of HR pathway mutations were 15.77 (95% CI: 1.571-158.4), patients with HR pathway mutations in bile cfDNA exhibited poorer overall survival (P = 0.0049). Our study suggests that bile cfDNA contains genome mutations and SVs, and HR pathway mutations in bile cfDNA can predict poor outcomes of CCA patients.

GenomicsVol. 116(5)
Second Military Medical University (CN), MemorialCare Health System (US), Eastern Hepatobiliary Surgery Hospital (CN)
Zero hunger
Openalex Percentile: Top 9%
Cholangiocarcinoma and Gallbladder Cancer Studies
2.86
DOIOpen Access PDFOpenAlex
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