# PDGFRA activating mutations in gastrointestinal stromal tumours

Source: https://onco.cc/key-papers/paper-heinrich-pdgfra-gist-science-2003/  
OnCo record `paper-heinrich-pdgfra-gist-science-2003` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

This study found that most gastrointestinal stromal tumours without KIT mutations instead carry activating mutations in the related receptor PDGFRA, including the D842V mutation that resists imatinib, completing the genetic definition of the disease.

## Summary

Mutation analysis of KIT-wild-type gastrointestinal stromal tumours identifying activating PDGFRA mutations in about a third, mutually exclusive with KIT mutations, with the mutant receptors showing constitutive activation and, for D842V, resistance to imatinib in vitro, while other PDGFRA mutants were sensitive.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: Science
- Year: 2003
- DOI: 10.1126/science.1079666
- Authors: Heinrich MC, Corless CL, Duensing A, et al.
- Findings: PDGFRA mutations in about 35 percent of KIT wild-type GISTs.; D842V mutant resistant to imatinib; other PDGFRA mutants sensitive.
- What it means: PDGFRA testing is part of standard GIST genotyping, and the imatinib resistance of D842V predicted here led to the development of avapritinib.
- Caveats: Discovery study; clinical resistance of D842V was confirmed in later trials.

## Sources

- Science 2003: https://doi.org/10.1126/science.1079666
- PubMed: https://pubmed.ncbi.nlm.nih.gov/12522257/

## Connected records

- cancers: [PDGFRA D842V-mutant GIST](https://onco.cc/cancers/gist-pdgfra-d842v/)
- journals: [Science](https://onco.cc/journals/science/)

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