FGFR2 Fusions or Rearrangements in Young Intrahepatic and Perihilar Cholangiocarcinoma Patients: Key Genetic Insights From a Pan‐Asian Study

作者：Yuta Maruki, Yasushi Yatabe, Chiharu Mizoguchi, Kathleen Yasmin de Almeida, Aumkhae Sookprasert, Charuwan Akewanlop, Ming‐Huang Chen, Ekaphop Sirachainan, Dao Van Tu, Rozita Abdul Malik, Chaiyut Charoentum, Hwoei Fen Soo Hoo, Suhana Yusak, Tsung‐Hao Liu, Rangasamy Ramachandran, Patrapim Sunpaweravong, Pei Jye Voon, Najihah Abu Bakar, Junki Mizusawa, Hitomi Sumiyoshi Okuma, Kenichi Nakamura, Chigusa Morizane, Takuji Okusaka · 发表于：Hepatology Research · 年份：2025 · DOI：10.1111/hepr.70031 · 被引用次数：1 · 研究领域：Cholangiocarcinoma and Gallbladder Cancer Studies、Fibroblast Growth Factor Research、Bladder and Urothelial Cancer Treatments

AIM: Biliary tract cancers, including intrahepatic cholangiocarcinoma (ICC), are aggressive with limited treatment options and poor prognosis. Recent trials (TOPAZ-1, Keynote-966) showed improved survival with ICIs plus gemcitabine and cisplatin. Targeted therapies, including FGFR inhibitors, are promising for cholangiocarcinoma patients with FGFR2 gene fusions or rearrangements, although few reports exist on FGFR2 positivity and clinical data in Asia. This study aims to address this gap by evaluating FGFR2 fusions or rearrangements in intrahepatic and perihilar cholangiocarcinoma patients across Asia, providing insights into their clinical significance and potential therapeutic implications. METHODS: This multicenter study evaluated the frequency of FGFR2 rearrangements and fusion genes in ICC and perihilar cholangiocarcinoma across Asia (Thailand, Malaysia, Vietnam, and Taiwan) using fluorescence in situ hybridization (FISH) and comprehensive genomic profiling with the Todai OncoPanel2 (TOP2). RESULTS: Of 113 patients, 102 were eligible; FGFR2 rearrangements/fusions were found in 3.9% (4 cases) by FISH, all of which were also confirmed by the TOP2 panel, consistent with the Japanese PRELUDE study. Younger age was significantly associated with FGFR2 positivity (34.5 ± 3.17 vs. 62.69 ± 1.04; p = 0.0003), whereas no correlation was observed with hepatitis infection, alcohol use, or smoking history. Genomic profiling identified frequent mutations in TP53, KRAS, and ARID1A with ...