Comprehensive analysis of genomic alterations of Chinese hilar cholangiocarcinoma patients

Int J Clin Oncol. 2021 Apr;26(4):717-727. doi: 10.1007/s10147-020-01846-z. Epub 2021 Jan 2.


Background: Cholangiocarcinoma (CCA) is a rare malignant tumor of the biliary system. The heterogeneity of CCA leads to the lack of effective targeted treatment for CCA subtypes. The molecular characteristic of hilar CCA (hCCA) is still unclear.

Methods: A total of 63 hCCA patients were enrolled from Shanghai Eastern Hepatobiliary Surgery Hospital. Formalin-fixed, paraffin-embedded tumor tissues, and matched blood were collected and deep sequencing targeting 450 cancer genes were performed. Tumor mutation burden (TMB) was measured by an algorithm developed in-house. Correlation analysis was performed by Fisher's exact test.

Results: The most commonly mutated genes were TP53 (51.7%), NF1 and KRAS (20%, for both), SMAD4 (16.7%), FAT3 and FRS2 (13.3%, for both), NF1 (11.7%), and KMT2C, MDM2, and ATM (10%, for each) in hCCA. ARID1A, GATA6, and PREX2 mutations commonly occurred in female and KMT2C mutations mainly occurred in patients under 60 years old. Statistical analysis showed the association between ARID1A mutation and tumor stage (P = 0.041) and between NF1 mutation and high TMB (P = 0.0095). Furthermore, ARID1B mutation was identified to associate with the poor prognosis of Chinese hCCA patients (P = 0.004).

Conclusion: The mutational characterization of hCCA is different from both extrahepatic CCA and intrahepatic CCA. ARID1B is a potential biomarker for prognosis prediction of Chinese hCCA patients.

Keywords: Biomarker; Cholangiocarcinoma; Disease-free survival; Genomic alteration; Tumor mutational burden.

MeSH terms

  • Bile Duct Neoplasms* / genetics
  • Bile Ducts, Intrahepatic
  • China
  • Cholangiocarcinoma* / genetics
  • Female
  • Genomics
  • Humans
  • Klatskin Tumor*
  • Middle Aged
  • Mutation