key papersKey paper
Gain-of-function mutations of c-kit in human gastrointestinal stromal tumours
This discovery that gastrointestinal stromal tumours carry activating mutations in the KIT receptor, and express KIT protein, defined the disease and provided the target for imatinib three years later.
Overview
Study showing KIT expression in gastrointestinal stromal tumours, identifying gain-of-function mutations in the KIT juxtamembrane domain (exon 11) in five of six tumours analysed, and demonstrating that the mutant receptors are constitutively activated and transforming, with interstitial cells of Cajal as the likely cell of origin.
Basic scienceChanged practice
Authors
Hirota S, Isozaki K, Moriyama Y, et al.
Published
Science, 1998
Findings
- Activating KIT juxtamembrane domain mutations in five of six GISTs.
- KIT protein expression as a diagnostic marker.
What it means
KIT immunohistochemistry and mutation testing define GIST, and the exon 11 mutations described here are the ones most sensitive to imatinib.
Caveats
- Small discovery series; PDGFRA mutations in KIT-negative GIST were found later.