The genomic profiles of patients with cholangiocarcinoma (CCA), who are 45 years of age and younger, are different than that of patients older than 45 years of age, found a new study published in the journal Cancer Biology and Therapy.
This finding is important for the provision of precision medicine.
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For the study, researchers from China analyzed a total of 188 patients with CCA. They divided the patients into 2 groups according to their age: young or 45 years and younger, and old or above age 45.
They then compared the somatic and germline mutation profiles, differentially enriched genetic alterations, and actionable genetic alterations between the 2 groups of patients. They used an external dataset of 392 patients to validate the molecular features and compare overall survival.
They found that KRAS alterations were more common among old patients compared to young patients. On the other hand, FGFR2 fusions were more common among young patients compared to old. Interestingly, TERT promoter mutations were only seen in old patients.
There were no significant differences in overall survival between young and old patients as shown using the external dataset. However, old patient-enriched KRAS and TERT alterations were associated with reduced overall survival.
Around 40% of patients had actionable oncogenic mutations suggesting they may respond to targeted therapy or immunotherapy.
Actionable FGFR2 fusions and BRAFV600E mutations were more common among young women with the disease compared to older patients.
The researchers also reported that the enrichment of KRAS/TERT alterations in old patients was associated with worse overall survival. They concluded that previously reported inferior survival in older patients with CCA may be explained by this.
CCA is the second most common primary hepatic malignancy, accounting for approximately 15% of primary liver tumors. There are several risk factors associated with CCA including smoking, alcohol consumption, obesity, hepatitis B and C virus infection, genetic alterations related to DNA repair, and certain drugs.
Reference
Wang J, Shi Y, Chen J, et al. Genomic profiling, prognosis, and potential interventional targets in young and old patients with cholangiocarcinoma. Published online June 19, 2023. doi: 10.1080/15384047.2023.2223375
