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FGFR2 fusions in iCCA

Genetic alterations of fibroblast growth factor receptor (FGFR) exist across different tumor types, including intrahepatic cholangiocarcinoma (iCCA)

FGFR has emerged as a tumorigenic driver in cancers such as iCCA, urothelial carcinoma, myeloid/lymphoid neoplasms, and other malignancies.1-3

Genetic alterations have been observed in all FGFR subtypes (FGFRl, FGFR2, FGFR3, and FGFR4). Alterations include point mutations, gene amplifications, and chromosomal rearrangements that may result in fusion proteins, including FGFR2 fusions.4

Image of table - Potential FGFR genetic alterations

In iCCA, FGFR2 fusions have been identified as key oncogenic drivers in 10% to 16% of patients7-9

FGFR2 fusions are found almost exclusively in iCCA.5,8 When they occur, they cause constitutive FGFR2 signaling, which in turn contributes to a variety of tumorigenic processes.10,11

Abnormal FGFR2 signaling pathway. FGFR2 fusions result in ligand-independent activation of downstream processes, leading to tumorigenesis10,11
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FGFR2 fusions are detectable early in disease progression, elevating the importance of identifying these alterations in patients at diagnosis.12

Along with FGFR2 fusions, other clinically significant alterations have been identified in iCCA

Clinically significant genomic alterations have been identified in ~50% of iCCA patients, enabling a more individualized picture of each patient's disease biology.5,9,13,14 The most common clinically significant genomic alterations include FGFR2 fusions and isocitrate dehydrogenase (IDH) mutations.9

Clinically significant genomic alterations are abundant in iCCA*

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Clinically significant genomic alterations are abundant in iCCA*

Percentages reported for individual alterations are from different primary analyses and are not all drawn from a single population of patients with iCCA.

*Although FGFR2 fusions and IDH mutations tend to be mutually exclusive in iCCA, mutations in the "other alterations" category can be found in tumors that also carry other clinically significant mutations or genetic alterations.

EGFR, epidermal growth factor receptor; KRAS, Kirsten rat sarcoma viral oncogene homolog; MSI-H, microsatellite instability-high; NTRK, neurotrophic tyrosine receptor kinase.

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