FGFR2 fusion/rearrangement analysis in intrahepatic cholangiocarcinoma using DNA/RNA-based NGS and FISH

作者：Xin Zhang, Qianming Bai, Yulin Wang, Zhengzeng Jiang, Jing Han, Xue Cheng, Kai Huang, Lijuan Luan, Xiaoyong Huang, Xiaowu Huang, Guo‐Ming Shi, Yingyong Hou, Yuan Ji · 发表于：Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · 年份：2025 · DOI：10.1007/s00428-025-04067-9 · 被引用次数：9 · 研究领域：Cholangiocarcinoma and Gallbladder Cancer Studies、Cancer-related molecular mechanisms research、MicroRNA in disease regulation

Patients with intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 fusion/rearrangement benefit from targeted therapies, highlighting the need for reliable testing strategies to identify FGFR2 alterations. We assessed 226 iCCA cases using RNA-based NGS, DNA-based NGS, and break-apart FISH to evaluate the effectiveness of these methods in detecting FGFR2 fusion/rearrangement. The detection rates for FGFR2 fusion/rearrangement were 9.7% (22/226) for RNA-based NGS, 7.1% (16/226) for DNA-based NGS, and 10.2% (23/226) for FISH. Among the 26 FGFR2 fusion/rearrangement-positive cases identified by any method, only 15 (57.7%) were positive by all three techniques, yielding a concordance rate of 95.1% (215/226). RNA-based NGS confirmed oncogenic FGFR2 fusion in 81% (21/26) of positive cases and identified five novel oncogenic fusions. Thirty-five percent (6/17) of the partner genes were located on chromosome 10, with BICC1 being the most common fusion partner, while the rest were distributed across the other 9 chromosomes. FISH demonstrated a sensitivity of 95.2% and specificity of 98.5%, compared to oncogenic FGFR2 fusions confirmed by RNA-based NGS, while DNA-based NGS exhibited a sensitivity of 71.4% and specificity of 99.5%, identifying FGFR2 mutations in 4 cases. FGFR2-FISH positive cases displayed no significant heterogeneity in positive cell distribution. Oncogenic FGFR2 fusion/rearrangement was associated with small duct type iCCA, especially in cases with positive serum HBs...