Genomic alterations characteristic of intrahepatic cholangiocarcinoma (iCCA) are well known. This study examined whether genomic alterations from a primary tumor would differ from metastatic tumor tissue and liquid biopsy in iCCA.1
Comprehensive genomic profiling was performed on 1268 tissue samples from patients with advanced-stage iCCA using the primary tumor in 1048 cases and the metastatic tumor from 220 cases and 364 liquid biopsy cases (solid tissue: 318-327 genes; liquid biopsy: 72 genes).1
Tumor mutational burden was determined on sequenced DNA. PD-L1 expression in tumor cells was measured by immunohistochemistry. Frequencies of untargetable genomic alterations were similar overall. IDH1 and FGFR2 genomic alterations known to be enriched in iCCA were less frequent in metastatic tumors than in primary tumors. Both IDH1 and FGFR2 genomic alterations were identified in liquid biopsy. Genomic alterations uncovered in primary tumors versus metastatic tumors in advanced iCCA were found to be significantly different, principally with the metastatic tumor cohort demonstrating greater KRAS and lower IDH1 and FGFR2 genomic alterations. This suggests that the metastatic tumor group may contain non-iCCA cases whose metastatic lesions were actually derived from other primary sites and incorrectly assigned the diagnosis of iCCA.
Liquid biopsy detected more IDH1 genomic alterations than metastatic tumor biopsy and also detected other potentially targetable alterations.
