Genomic alterations (mutations) characteristic of intrahepatic cholangiocarcinoma (CCA) are well-known. In this study, Jeffrey S. Ross, MD, Medical Director, Foundation Medicine, Cambridge, Massachusetts, and colleagues examined whether genomic alterations in intrahepatic CCA of a primary tumor would differ from those found in tissue from a tumor that has metastasized (spread) to other parts of the body and the alterations that are found with liquid biopsy (a test done using a blood sample). Dr. Ross presented the study results at the 2020 ASCO annual meeting.
Comprehensive genomic profiling was performed on 1268 tissue samples from patients with advanced-stage intrahepatic CCA using the primary tumor in 1048 cases, a metastatic tumor from 220 cases, and liquid biopsy in 364 cases.
Tumor mutational burden was determined on sequenced DNA. The expression of PD-L1 protein on tumor cells was measured by biomarker testing. The frequencies of untargetable genomic alterations (for which no drug therapies are yet available) found in those samples were similar overall.
IDH1 and FGFR2 are 2 genomic mutations often found in intrahepatic CCA; these were less often seen in metastatic tumors than in primary tumors. Both IDH1 and FGFR2 genomic alterations were identified by a liquid biopsy.
Genomic alterations uncovered in primary tumors rather than in metastatic tumors in advanced intrahepatic CCA were significantly different, principally with the patients with metastatic tumor demonstrating more KRAS and fewer IDH1 and FGFR2 genomic alterations.
This finding suggests that the metastatic tumor group might have included cases that were not intrahepatic CCA, and their metastatic lesions were derived from other primary sites and were incorrectly assigned the diagnosis of intrahepatic CCA.
Liquid biopsy detected more IDH1 genomic mutations than a biopsy of metastatic tumors, and detected other potentially targetable alterations as well.
