• What is PDGFRA?
  • PDGFRA Exon 12 Mutation
  • Clinical Trials


The platelet derived growth factor receptor alpha (PDGFRA) belongs to a family of receptor tyrosine kinases (RTKs) that include PDGFRA and PDGFRB. The binding of ligands, such as platelet derived growth factor (PDGF), induces a conformational change that facilitates receptor homo- or heterodimer formation, thereby resulting in activation of PDGFRA tyrosine kinase activity. Activated PDGFRA then phosphorylates its substrates, resulting in activation of multiple downstream pathways within the cell, including the PI3K-AKT-mTOR pathway, which is involved in cell survival, and the RAS-RAF-MEK-ERK pathway, which is involved in cell proliferation (Figure 1).

Mutant PDGFRA has been implicated in the pathogenesis of a number of cancers. For example, mutations are found in gastrointestinal stromal tumors (GIST; Corless et al. 2005Heinrich et al. 2003), and fusions are found in hypereosinophilic syndrome (Cools et al. 2003). In dermatofibrosarcoma protuberans, PDGFRA is activated by a PDGFB fusion protein; as a result, imatinib, as a PDGFRA inhibitor, has shown activity and is approved for clinical use (Labropoulos and Razis 2007; Simon et al. 1997).



Figure 1.
Schematic of PDGFRA signaling pathways. The binding of the ligand, platelet-derived growth factor (PDGF), to the PDGFRA receptor tyrosine kinase results in activation of the MAPK signaling pathway (RAS-RAF-MEK-ERK) and the PI3K pathway (PI3K-AKT-mTOR). The letter "K" within the schema denotes the tyrosine kinase domain.

Related Pathways

Contributors: Robert G. Maki, M.D., Ph.D., FACP, Vicki Keedy, M.D., M.S.C.I.

Suggested Citation: Maki, R., V. Keedy. 2016. PDGFRA. My Cancer Genome https://www.padiracinnovation.org/content/disease/gist/pdgfra/?tab=0 (Updated May 26).

Last Updated: May 26, 2016


PDGFRA is mutated in ~5% of GIST, most frequently in gastric GIST. Specifically, PDGFRA mutations are found mostly in exons 18 (tyrosine kinase 2 (TK2) domain; ~5%), 12 (juxtamembrane domain; 1%) and 14 (tyrosine kinase 1 (TK1) domain; <1%). Mutations except for D842V in exon 18 are sensitive to imatinib (Corless et al. 2005).


Contributors: Robert G. Maki, M.D., Ph.D., FACP, Vicki Keedy, M.D., M.S.C.I.

Suggested Citation: Maki, R., V. Keedy. 2015. PDGFRA in GIST. My Cancer Genome https://www.padiracinnovation.org/content/disease/gist/pdgfra/ (Updated June 18).

Last Updated: June 18, 2015

PDGFRA Exon 12 Mutation in GIST

Location of mutation juxtamembrane domain (V561D most common)
Frequency of PDGFRA mutations in GIST ~5% (Corless et al. 2005)
Frequency of PDGFRA exon 12 mutations in PDGFRA-mutated GIST 1% (Corless et al. 2005)
Implications for Targeted Therapeutics
Response to imatinib Confers increased sensitivity
Response to sunitinib Confers sensitivity in vitro
Response to sorafenib Unknown at this time
Response to nilotinib Unknown at this time
Response to dasatinib Unknown at this time

In vitro studies of PDGFRA exon 12 mutations suggest sensitivity to imatinib and most reported patients have had responses (Heinrich et al. 2003). Too few patients have been included in clinical trials to have an accurate understanding of their response to treatment with either imatinib or sunitinib.

Although exon specific data is not available, one year of adjuvant imatinib significantly improves relapse free survival for patients with non-D842V PDGFRA-mutated GIST (Corless et al. 2010). The survival of patients did not appear to be different if adjuvant therapy was given or not. There are no specific recommendations on the potential benefit of 3 years adjuvant imatinib vs 1 year imatinib for patients with PDGFRA mutations; these data are immature (Joensuu et al. 2011).


Figure 1.
Schematic of PDGFRA. Domains encoded by various exons are shown.

Contributors: Robert G. Maki, M.D., Ph.D., FACP, Vicki Keedy, M.D., M.S.C.I.

Suggested Citation: Maki, R., V. Keedy. 2015. PDGFRA Exon 12 Mutation in GIST. My Cancer Genome https://www.padiracinnovation.org/content/disease/gist/pdgfra/48/ (Updated March 5).

Last Updated: March 5, 2015

My Cancer Genome has released its new and improved cancer clinical trials search tool on our beta website. Please visit beta.padiracinnovation.org to check it out!

Disclaimer: The information presented at padiracinnovation.org is compiled from sources believed to be reliable. Extensive efforts have been made to make this information as accurate and as up-to-date as possible. However, the accuracy and completeness of this information cannot be guaranteed. Despite our best efforts, this information may contain typographical errors and omissions. The contents are to be used only as a guide, and health care providers should employ sound clinical judgment in interpreting this information for individual patient care.