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Updated: Feb 8, 2026

Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
FGFR3-TACC3 is an oncogenic fusion protein in respiratory epithelium
Sarah A Best1,2, Cassandra R Harapas1, Ariena Kersbergen1
1ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.
Abstract:
Structural rearrangements of the genome can drive lung tumorigenesis through the generation of fusion genes with oncogenic properties. Advanced genomic approaches have identified the presence of a genetic fusion between fibroblast growth factor receptor 3 (FGFR3) and transforming acidic coiled-coil 3 (TACC3) in non-small cell lung cancer (NSCLC), providing a novel target for FGFR inhibition. To interrogate the functional consequences of the FGFR3-TACC3 fusion in the transformation of lung epithelial cells, we generated a novel transgenic mouse model that expresses FGFR3-TACC3 concomitant with loss of the p53 tumor suppressor gene. Intranasal delivery of an Ad5-CMV-Cre virus promoted seromucinous glandular transformation of olfactory cells lining the nasal cavities of FGFR3-TACC3 (LSL-F3T3) mice, which was further accelerated upon loss of p53 (LSL-F3T3/p53). Surprisingly, lung tumors failed to develop in intranasally infected LSL-F3T3 and LSL-F3T3/p53 mice. In line with these observations, we demonstrated that intranasal delivery of Ad5-CMV-Cre induces widespread Cre-mediated recombination in the olfactory epithelium. Intra-tracheal delivery of Ad5-CMV-Cre into the lungs of LSL-F3T3 and LSL-F3T3/p53 mice, however, resulted in the development of lung adenocarcinomas. Taken together, these findings provide in vivo evidence for an oncogenic function of FGFR3-TACC3 in respiratory epithelium.
Insights
The fibroblast growth factor receptor 3-transforming acidic coiled-coil 3 (FGFR3-TACC3) fusion drives lung cancer. This study shows FGFR3-TACC3 causes lung adenocarcinoma in mice, but not nasal tumors.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Genomic rearrangements, including fusion genes, are key drivers of lung tumorigenesis.
- The FGFR3-TACC3 fusion gene has been identified in non-small cell lung cancer (NSCLC), presenting a potential therapeutic target for FGFR inhibitors.
Purpose of the Study:
- To investigate the functional role of the FGFR3-TACC3 fusion in lung epithelial cell transformation.
- To establish and utilize a novel transgenic mouse model to study the oncogenic effects of FGFR3-TACC3, in conjunction with p53 tumor suppressor gene loss.
Main Methods:
- Generation of a transgenic mouse model expressing FGFR3-TACC3 (LSL-F3T3) and its combination with p53 loss (LSL-F3T3/p53).
- Administration of Ad5-CMV-Cre virus via intranasal and intra-tracheal routes to induce gene recombination.
- Histopathological analysis of nasal cavities and lungs to assess tumor development and cellular transformation.
Main Results:
- Intranasal viral delivery induced glandular transformation in olfactory cells but not lung tumors in both LSL-F3T3 and LSL-F3T3/p53 mice.
- Intra-tracheal viral delivery into the lungs of LSL-F3T3 and LSL-F3T3/p53 mice led to the development of lung adenocarcinomas.
- Cre-mediated recombination was confirmed in the olfactory epithelium following intranasal delivery.
Conclusions:
- The FGFR3-TACC3 fusion gene possesses oncogenic properties in respiratory epithelium.
- The location of gene activation (nasal vs. lung) influences tumor development, with direct lung targeting being crucial for adenocarcinoma formation.
- This study provides in vivo validation of FGFR3-TACC3 as an oncogene in lung cancer.
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