# Gain-of-function mutations of c-kit in human gastrointestinal stromal tumours

Source: https://onco.cc/key-papers/paper-hirota-kit-gist-science-1998/  
OnCo record `paper-hirota-kit-gist-science-1998` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: Science
- Year: 1998
- DOI: 10.1126/science.279.5350.577
- Authors: Hirota S, Isozaki K, Moriyama Y, et al.
- 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.

## Sources

- Science 1998: https://doi.org/10.1126/science.279.5350.577
- PubMed: https://pubmed.ncbi.nlm.nih.gov/9438854/

## Connected records

- cancers: [KIT exon 11-mutant GIST](https://onco.cc/cancers/gist-kit-exon-11/)
- journals: [Science](https://onco.cc/journals/science/)

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