Editors' ChoiceCancer Biology

Two Means to a Bad End

STKE  04 Feb 2003:
Vol. 2003, Issue 168, pp. tw55-TW55
DOI: 10.1126/stke.2003.168.tw55

Gastrointestinal stromal tumors (GISTs) have recently attracted much attention because they are exceptionally sensitive to the new cancer drug Gleevec, which inhibits the oncogenic KIT receptor tyrosine kinase that is aberrantly expressed in many of these tumors. Heinrich et al. have now examined GISTs with normal KIT function and find that these tumors harbor activating mutations in a gene that encodes a related tyrosine kinase, platelet-derived growth factor receptor-A (PDGFRA). Tumors with mutations in KIT or PDGFRA have similar cytogenetic profiles and display activation of the same downstream signaling pathways. These results reinforce the notion that mutations in distinct genes can activate common cellular pathways that drive cancer development.

M. C. Heinrich, C. L. Corless, A. Duensing, L. McGreevey, C.-J. Chen, N. Joseph, S. Singer, D. J. Griffith, A. Haley, A. Town, G. D. Demetri, C. D. M. Fletcher, J. A. Fletcher, PDGFRA activating mutations in gastrointestinal stromal tumors. Science 299, 708-710 (2003). [Abstract] [Full Text]