FGFR3-TACC3 is an oncogenic fusion protein in respiratory epithelium
Sarah A Best, Cassandra R Harapas, Ariena Kersbergen, Vivek Rathi, Marie-Liesse Asselin-Labat, Kate D Sutherland
ONCOGENE | NATURE PUBLISHING GROUP | Published : 2018
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 seromuci..View full abstract
Awarded by Worldwide Cancer Research Project Grant
Awarded by Victorian Cancer Agency (VCA) Early Career Seed Grant
We are grateful to C. Alvarado, L. Scott, H. Johnson, K. Birchall, and L. Mackiewicz for animal husbandry, E. Tsui and C. Tsui in the WEHI Histology Facility for expert support and P. Maltezos for preparation of the nasal cavity graphic image. The authors thank T. Wilson, J. Mighall, and J. Pasquet for technical support and W. Alexander for useful discussions and critically reading the manuscript. This work was supported in part by a Worldwide Cancer Research Project Grant [14-0433]. SAB is supported by a Victorian Cancer Agency (VCA) Early Career Seed Grant (ECSG16001); M-LA-L is supported by a Viertel Foundation Senior Medical Research Fellowship; KDS is supported by the Peter and Julie Alston Centenary Fellowship. This work was made possible through Victorian Government Operational Infrastructure Support and Australian Government.