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<p>Patients with intrahepatic cholangiocarcinoma (iCCA) harboring <i>FGFR2</i> fusion/rearrangement benefit from targeted therapies, highlighting the need for reliable testing strategies to identify <i>FGFR2</i> 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 <i>FGFR2</i> fusion/rearrangement. The detection rates for <i>FGFR2</i> 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 <i>FGFR2</i> 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 <i>FGFR2</i> 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 <i>BICC1</i> 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 <i>FGFR2</i> fusions confirmed by RNA-based NGS, while DNA-based NGS exhibited a sensitivity of 71.4% and specificity of 99.5%, identifying <i>FGFR2</i> mutations in 4 cases. <i>FGFR2</i>-FISH positive cases displayed no significant heterogeneity in positive cell distribution. Oncogenic <i>FGFR2</i> fusion/rearrangement was associated with small duct type iCCA, especially in cases with positive serum HBsAg and absent cholangiolocarcinoma components and peripheral liver steatosis. This study provides a comprehensive comparison of three assays for detecting <i>FGFR2</i> fusion/rearrangement, along with clinicopathologic characterization of oncogenic <i>FGFR2</i> fusion in iCCA.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月8日

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  • Xin Zhang,
  • Qianming Bai,
  • Yulin Wang,
  • Zhengzeng Jiang,
  • Jing Han,
  • Cheng Xue,
  • Kai Huang,
  • Lijuan Luan,
  • Xiaoyong Huang,
  • Xiaowu Huang,
  • Guoming Shi,
  • Yingyong Hou,
  • Yuan Ji

摘要

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 HBsAg and absent cholangiolocarcinoma components and peripheral liver steatosis. This study provides a comprehensive comparison of three assays for detecting FGFR2 fusion/rearrangement, along with clinicopathologic characterization of oncogenic FGFR2 fusion in iCCA.