PDGFRA

Overview

PDGFRA encodes platelet-derived growth factor receptor alpha; activating mutations and amplifications drive a subset of GIST and gliomas.

Alterations observed in the corpus

  • Focal PDGFRA amplifications (along with CDK4 and MYCN) were used to define “molecular grade-intermediate” in 1p19q intact IDH-mutant astrocytomas in a 128-patient MSKCC active-surveillance cohort PMID:37910594.
  • PDGFRA is a co-primary GIST driver; KIT/PDGFRA wild-type cases with SDHB IHC loss were classified as SDH-deficient in the MSK GIST genomic risk model cohort PMID:37477937.
  • PDGFRA amplification was detected exclusively in sporadic ANGS but absent in radiation-associated (RT) angiosarcoma (n=44 RT-AS, n=135 sporadic AS) in the MSK RT-sarcoma comparative genomic study PMID:37350195.
  • Expression marker in neuroblastoma: PDGFRA is significantly expressed in both the undifferentiated nC3 cluster and the mesenchymal stromal (MSC) nC1 cluster of high-risk neuroblastoma tumors in a single-nuclei RNA-seq study of 11 tumors; RNAscope validated absence in low-risk stage 4S tumors. PMID:34493726
  • PDGFRA cited as a known GIST driver alongside KIT; the KIT/PDGFRA → imatinib paradigm was explicitly invoked as the model for genotype-directed sarcoma therapy in a 207-patient multi-subtype sarcoma sequencing study (sarc_mskcc) PMID:20601955.
  • Mutated in LUAD (TSP, n=188); co-occurrence with NTRK2 and FGFR4 mutations noted; receptor tyrosine kinase. PMID:18948947
  • Somatic mutations in 10% of GISTs in a paired tumor-normal sequencing study PMID:36593350
  • PDGFRA amplification detected in lung squamous cell carcinoma (TCGA, 178 tumors) PMID:22960745
  • Copy number amplification in Basal-like breast cancer; identified as a potential druggable target in TCGA 510-tumor cohort PMID:23000897
  • Focal amplification in 13.1% of GBM; intragenic Δ8,9 splice variant and novel Δ2–7 identified; concurrent with EGFR alteration in 42.4% of PDGFRA-altered cases PMID:24120142
  • High PDGFRA expression cited as a rationale for sunitinib therapy in metastatic NEN patients PN2 and PN10 in a WGTA precision-oncology study PMID:24326773
  • Single nasal-cavity case with missense p.Thr674Ile (AF 8%); the patient received targeted therapy with imatinib and was NED at 19 months — the only AdCC patient in the cohort to receive targeted therapy PMID:24418857
  • Recurrently mutated in rhabdomyosarcoma at 1.4% frequency (PFN-enriched); classified as a receptor tyrosine kinase driver PMID:24436047
  • Implicated in HCC pathogenesis as part of the receptor tyrosine kinase landscape; sorafenib inhibits PDGFR alongside VEGFR/RAF as part of its multi-kinase mechanism in advanced HCC PMID:24798001
  • PDGFRA expression positively correlates with stromal SEMA7A in GBC (scRNA-seq, GEO datasets), co-marking cancer-associated fibroblast (CAF) subpopulations alongside ACTA2, MFAP5, TGFBR1, and TGFBR2; high stromal SEMA7A associates with lymph node metastasis and poor OS in a GBC cohort (n=86) PMID:24997986
  • In cutaneous melanoma (SKCM), PDGFRA is co-amplified with KIT and KDR at 4q12 in the Triple-WT subtype (no hot-spot BRAF/RAS/NF1); focal amplification enriched in Triple-WT. imatinib, sorafenib, and crenolanib are nominated therapeutic candidates. PMID:26091043
  • Identified as a marker of one of the three ILC mRNA subtypes in a comprehensive molecular analysis of invasive lobular carcinoma; associated with subtype-specific expression patterns PMID:26451490
  • Amplification of the PDGFRA/KIT/KDR locus was significantly enriched in oncogene-negative lung ADC (242 cases lacking known RTK/Ras/Raf activating events), nominating this locus as a candidate driver in this subset (q < 0.25); inclusion of this locus in the RTK/Ras/Raf driver pool raised the proportion of lung ADCs with a candidate driver to 76% overall. PMID:27158780
  • Co-amplification of PDGFRA, KDR, and KIT observed in 4 adenoid cystic carcinoma (ACYC) patients treated with regorafenib in a recurrent/metastatic head and neck cancer NGS cohort PMID:27442865.
  • Overexpression in osteosarcoma (OS); identified as a multi-targeted kinase inhibitor (MTKI) target in a pediatric precision-oncology cohort PMID:28007021
  • Significantly enriched in the unmatched driver (UMD) cohort vs level 1-4 patients in a prospective LUAD study (860 patients, MSK-IMPACT panel) PMID:28336552

Cancer types (linked)

  • ASTR / DIFG — focal amplification marks intermediate molecular grade in IDH-mutant astrocytoma PMID:37910594.
  • GIST — co-primary driver alongside KIT PMID:37477937.
  • ANGS — PDGFRA amplification exclusive to sporadic AS, absent in RT-AS PMID:37350195.
  • NBL — expressed in undifferentiated nC3 and MSC nC1 clusters; co-expressed with PRRX1 and YAP1 as mesenchymal markers; absent in low-risk 4S tumors by RNAscope. PMID:34493726

Co-occurrence and mutual exclusivity

Therapeutic relevance

Open questions

  • Whether PDGFRA amplification should upgrade IDH-mutant LGG molecular grade is unresolved PMID:37910594.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:18948947

This page was processed by crosslinker on 2026-05-14. - PMID:36593350

This page was processed by crosslinker on 2026-05-14. - PMID:22960745

This page was processed by crosslinker on 2026-05-14. - PMID:23000897

This page was processed by crosslinker on 2026-05-14. - PMID:24120142

This page was processed by crosslinker on 2026-05-14. - PMID:24326773

This page was processed by crosslinker on 2026-05-14. - PMID:24418857

This page was processed by crosslinker on 2026-05-14. - PMID:24436047

This page was processed by crosslinker on 2026-05-14. - PMID:24798001

This page was processed by crosslinker on 2026-05-14. - PMID:24997986

This page was processed by crosslinker on 2026-05-14. - PMID:26091043

This page was processed by crosslinker on 2026-05-14. - PMID:26451490

This page was processed by crosslinker on 2026-05-14. - PMID:27158780

This page was processed by entity-page-writer on 2026-05-15. - PMID:27442865

This page was processed by entity-page-writer on 2026-05-15. - PMID:28007021

This page was processed by wiki-cli on 2026-05-14. - PMID:28336552

This page was processed by wiki-cli on 2026-05-14.