Researchers developed a rapid and robust assay based on fluorescent in situ hybridization (FISH) to detect FGFR2 translocations in intrahepatic cholangiocarcinoma (iCCA). They validated the assay using archival formalin-fixed paraffin-embedded specimens.
“Compared to [next generation sequencing], the FISH assay may have potential advantages in clinical applications such as a shorter turnaround time, less consumption of tissue samples, more tolerance to sample pre-analytical conditions and spatial resolving of translocations,” the researchers wrote.
They also identified a novel FGFR2 translocation involving the SHROOM3 gene using the assay. The study is published in the journal Diagnostics.
The team led by Steve Anderson, PhD, from Labcorp Drug Development evaluated the analytical performance of the assay for probe localization, probe sensitivity and specificity, and assay precision using 25 archival formalin-fixed paraffin-embedded specimens from local iCCA patients. They tested the patients for FGFR2 translocations using the assay.
The results of FISH correlated with those of next-generation sequencing on some samples. The novel FGFR2 translocation that was identified was t(4;10) (q21;q26).
Read more about CCA subtypes
CCA is a heterogeneous group of rare malignant tumors that originate from cells of the biliary tree. Based on their origin, there are 3 different subtypes of CCA. iCCA originates from inside the hepatic parenchyma and can occur anywhere in the intrahepatic biliary tree. Perihilar CCA (pCCA) is localized in the biliary tree, proximal to the origin of the cyst duct. Distal CCA is anatomically distinct from pCCA by the insertion of the cystic duct.
FGFR fusions that retain the FGFR kinase domain are active kinases that are either overexpressed or constitutively activated throughout diverse cancer types including CCA.
FISH is a cytogenetic technique that uses fluorescent DNA probes to target specific locations on chromosomes, resulting in colored signals that can be detected using a fluorescent microscope. Like next-generation sequencing, it has been used as an effective tool to investigate translocations with multiple or unknown translocation partners.
Zhang L, Zheng H, Xu L, et al. A robust FISH assay to detect FGFR2 translocations in intrahepatic cholangiocarcinoma patients. Diagnostics (Basel). 2023;16;13(12):2088. doi:10.3390/diagnostics13122088