Editors' ChoiceCancer

Oncogenic TACC-tics

Sci. Signal.  11 Sep 2012:
Vol. 5, Issue 241, pp. ec238
DOI: 10.1126/scisignal.2003587

Human cancers exhibit many types of genomic rearrangements—including some that juxtapose sequences from two unrelated genes—thereby creating fusion proteins with oncogenic activity. Functional analysis of these fusion genes can provide mechanistic insights into tumorigenesis and potentially lead to effective drugs, as famously illustrated by the BCR-ABL gene in chronic myelogenous leukemia. Singh et al. identify and characterize a fusion gene present in 3% of human glioblastomas, a deadly brain cancer. In the resultant fusion protein, the tyrosine kinase region of the fibroblast growth factor receptor (FGFR) is joined to a domain from a transforming acidic coiled-coil (TACC) protein. The TACC-FGFR protein is oncogenic, shows unregulated kinase activity, localizes to the mitotic spindle, and disrupts chromosome segregation. In mice, FGFR inhibitors slowed the growth of tumors driven by the TACC-FGFR gene, suggesting that a subset of glioblastoma patients may benefit from these types of drugs.

D. Singh, J. M. Chan, P. Zoppoli, F. Niola, R. Sullivan, A. Castano, E. M. Liu, J. Reichel, P. Porrati, S. Pellegatta, K. Qiu, Z. Gao, M. Ceccarelli, R. Riccardi, D. J. Brat, A. Guha, K. Aldape, J. G. Golfinos, D. Zagzag, T. Mikkelsen, G. Finocchiaro, A. Lasorella, R. Rabadan, A. Iavarone, Transforming fusions of FGFR and TACC genes in human glioblastoma. Science 337, 1231–1235 (2012). [Abstract] [Full Text]