First proficiency testing for <scp>NGS</scp>‐based and combined <scp>NGS</scp>‐ and <scp>FISH</scp>‐based detection of <scp><i>FGFR2</i></scp> fusions in intrahepatic cholangiocarcinoma

Neumann, Olaf; Lehmann, Ulrich; Bartels, Stephan; Pfarr, Nicole; Albrecht, Thomas; Ilm, Katharina; Christmann, Jens; Volckmar, Anna‐Lena; Goldschmid, Hannah; Kirchner, Martina; Allgäuer, Michael; Walker, Maria; Kreipe, Hans; Tannapfel, Andrea; Weichert, Wilko; Schirmacher, Peter; Kazdal, Daniel

doi:10.1002/cjp2.308

Cited by 4 publications

(3 citation statements)

References 22 publications

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“…There are several issues in terms of the sensitivity of the assays for FGFR2 genetic alterations using next-generation sequencing (NGS) or FISH [ 14 ], since over 150 genes have been identified as fusion partner with FGFR2 [ 12 , 16 ]. We tried to detect several common FGFR2 fusions by using the FGFR2-fusion-specific primers.…”

Section: Discussionmentioning

confidence: 99%

“…Accumulating data suggest that about a half of iCCAs have targetable genetic alterations [ 8 , 9 ]. The fibroblast growth factor receptor 2 (FGFR2), which is one of four FGFR family members that encode transmembrane receptor tyrosine kinases, has attracted much attention [ 10 – 14 ]. The FGFR2 fusions or rearrangements are found as genetic abnormalities in 10–20% of iCCA, especially in small duct-type iCCAs [ 10 – 12 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

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Expression of fibroblast growth factor receptor 2 (FGFR2) in combined hepatocellular-cholangiocarcinoma and intrahepatic cholangiocarcinoma: clinicopathological study

Sasaki,

Sato,

Nakanuma

2024

Virchows Arch

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Genetic alterations including fusions in fibroblast growth factor receptor 2 (FGFR2) are detected in 10–20% of intrahepatic cholangiocarcinoma (iCCA), and FGFR2 inhibitors are effective for the treatment of iCCA. We examined a prevalence of FGFR2 genetic alterations and their clinicopathological significance in combined hepatocellular–cholangiocarcinoma (cHCC-CCA). FGFR2 expression, which is a surrogate marker for FGFR2 genetic alterations, was immunohistochemically assessed in the liver sections from 75 patients with cHCC-CCA, 35 with small duct-type iCCA, 30 with large duct-type iCCA, and 35 with hepatocellular carcinoma (HCC). FGFR2 genetic alterations were detected by reverse transcription-PCR and direct sequence. An association of FGFR2 expression with clinicopathological features was investigated in cHCC-CCAs. FGFR2 expression was detected in significantly more patients with cHCC-CCA (21.3%) and small duct-type iCCA (25.7%), compared to those with large duct-type iCCA (3.3%) and HCC (0%) (p < 0.05). FGFR2-positive cHCC-CCAs were significantly smaller size (p < 0.05), with more predominant cholangiolocarcinoma component (p < 0.01) and less nestin expression (p < 0.05). Genetic alterations of ARID1A and BAP1 and multiple genes were significantly more frequent in FGFR2-positive cHCC-CCAs (p < 0.05). 5′/3′ imbalance in FGFR2 genes indicating exon18-truncated FGFR2 was significantly more frequently detected in FGFR2-positive cHCC-CCAs and small duct iCCAs, compared to FGFR2-negative ones (p < 0.05). FGFR2::BICC fusion was detected in a case of cHCC-CCAs. FGFR2 genetic alterations may be prevalent in cHCC-CCAs as well as small duct-type iCCAs, which suggest cHCC-CCAs may also be a possible therapeutic target of FGFR2 inhibitors. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expression of fibroblast growth factor receptor 2 (FGFR2) in combined hepatocellular-cholangiocarcinoma and intrahepatic cholangiocarcinoma: clinicopathological study

Sasaki,

Sato,

Nakanuma

2024

Virchows Arch

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“…Reliable and accurate detection of these fusions is critical, but at present, real-world data on the performance of validated techniques are limited. Both fluorescence in situ hybridization and RNA-based next-generation sequencing are accepted tests [97]. Diversely, bemarituzumab showed the greatest efficacy in FGFR2b-overexpressed GC and EJC tested with IHC.…”

Section: Discussionmentioning

confidence: 99%

Targeting FGFR Pathways in Gastrointestinal Cancers: New Frontiers of Treatment

Ratti,

Orlandi,

Hahne

et al. 2023

Biomedicines

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In carcinogenesis of the gastrointestinal (GI) tract, the deregulation of fibroblast growth factor receptor (FGFR) signaling plays a critical role. The aberrant activity of this pathway is described in approximately 10% of gastric cancers and its frequency increases in intrahepatic cholangiocarcinomas (iCCAs), with an estimated frequency of 10–16%. Several selective FGFR inhibitors have been developed in the last few years with promising results. For example, targeting the FGFR pathway is now a fundamental part of clinical practice when treating iCCA and many clinical trials are ongoing to test the safety and efficacy of anti-FGFR agents in gastric, colon and pancreatic cancer, with variable results. However, the response rates of anti-FGFR drugs are modest and resistances emerge rapidly, limiting their efficacy and causing disease progression. In this review, we aim to explore the landscape of anti-FGFR inhibitors in relation to GI cancer, with particular focus on selective FGFR inhibitors and drug combinations that may lead to overcoming resistance mechanisms and drug-induced toxicities.

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FGFR2 fusions assessed by NGS, FISH, and immunohistochemistry in intrahepatic cholangiocarcinoma

Cao,

Yang,

Liu

et al. 2024

J Gastroenterol

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First proficiency testing for NGS‐based and combined NGS‐ and FISH‐based detection of FGFR2 fusions in intrahepatic cholangiocarcinoma

Cited by 4 publications

References 22 publications

Expression of fibroblast growth factor receptor 2 (FGFR2) in combined hepatocellular-cholangiocarcinoma and intrahepatic cholangiocarcinoma: clinicopathological study

Expression of fibroblast growth factor receptor 2 (FGFR2) in combined hepatocellular-cholangiocarcinoma and intrahepatic cholangiocarcinoma: clinicopathological study

Targeting FGFR Pathways in Gastrointestinal Cancers: New Frontiers of Treatment

FGFR2 fusions assessed by NGS, FISH, and immunohistochemistry in intrahepatic cholangiocarcinoma

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