Background: Cholangiocarcinoma (CCA), which consists of intrahepatic CCA (iCCA), perihilar CCA (pCCA), and distal CCA (dCCA), is an aggressive malignancy worldwide. PCCA and dCCA are often classified as extrahepatic CCA (exCCA). However, the differences in mutational characteristics between pCCA and dCCA remain unclear.
Methods: Deep sequencing targeting of 450 cancer genes was performed for genomic alteration detection. The tumor mutational burden (TMB) was measured by an algorithm developed in-house. Correlation analysis was conducted using Fisher's exact test.
Results: and mutations mainly occurred in iCCA and exCCA, respectively. In exCCA, the frequencies of , , , , and mutations were significantly higher in pCCA compared to dCCA, while the frequencies of and mutations were markedly lower in pCCA than those in dCCA. The prognosis-related mutations were different among the CCA subtypes. mutation was associated with short disease-free survival (DFS) and overall survival (OS), and mutation was associated with short DFS in dCCA patients. Meanwhile, mutation was associated with long DFS and OS, and mutation was associated with short DFS in pCCA. A series of mutations in genes, including , , , , and were found to be associated with the TMB.
Conclusions: In this study, we investigated the comprehensive genomic characterizations of CCA patients, identified the significant alterations in each subtype, and identified potential biomarkers for prognosis prediction. These results provide molecular evidence for the heterogeneity of CCA subtypes and evidence for further precision targeted therapy of CCA patients.
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| http://dx.doi.org/10.21037/jgo-21-776 | DOI Listing |
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