A new study published in the scientific journal Open Life Sciences showed frequent common mutations in the TP53 and KRAS genes in patients with intrahepatic cholangiocarcinoma (iCCA). These mutations were significantly associated with poor prognosis. 

The study also found that a high tumor mutation burden correlated with a mutation in DNA damage response and repair genes and homologous recombination repair genes. 

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“These results indicated that certain genomic alterations contribute to the clinical heterogeneity of iCCA,” the researchers wrote. “However, further research with larger sample sizes is required for a more comprehensive and deeper understanding of the molecular mechanisms underlying the development of this cancer.”

To shed light on the genetic features of iCCA, a team of researchers analyzed 12 patients with iCCA.

The investigators sequenced the tumor tissues from the patients using next-generation sequencing of a multigenes panel. They then analyzed the mutated genes, tumor mutation burden, and copy number variants in the sample. They also performed a pathway enrichment analysis. 

The results showed that the median tumor mutation burden was 2.76 mutations per megabase among the patients. The most commonly mutated genes were KRAS and TP53 and the comutations of KRAS and TP53 were seen in 2 of the 12 patients (16.7%). Importantly, the patient who had the highest tumor mutation burden did not have a mutation in either the KRAS or the TP53 gene. 

The researchers also reported that alterations in the TP53 and/or KRAS genes were significantly associated with poor progression-free survival. 

“In conclusion, we found that certain genetic mutations of TP53 and KRAS could predict poor prognosis in [patients with iCCA],” the researchers wrote. 


Peng J, Fang S, Li M, et al. Genetic alterations of KRAS and TP53 in intrahepatic cholangiocarcinoma associated with poor prognosis. Open Life Sci. Published online July 17, 2023. doi:10.1515/biol-2022-0652