PDGF receptor mutations in human diseases

Guérit, Emilie M; Arts, Florence A; Dachy, Guillaume; Boulouadnine, Boutaina; Demoulin, Jean‐Baptiste

doi:10.1007/s00018-020-03753-y

Cited by 69 publications

(57 citation statements)

References 134 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PDGFRA, a classical proto-oncogene that encodes receptor tyrosine kinases that respond to plateletderived growth factor (PDGF), was recently identified to impact the formation of the neural crest [38] .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

JUN and PDGFRA as Crucial Candidate Genes for Childhood Autism Spectrum Disorder

Wang

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that is characterized by marked genetic heterogeneity. This study aimed to use gene expression datasets to explore candidate hub genes for ASD. Methods: In this study, two independent microarray datasets of the cerebellum of children with ASD were integratively analysed using NetworkAnalyst to screen crucial candidate genes and related signalling pathways. Upregulation of the two hub genes was validated by other datasets and an ASD mouse model. Results: NetworkAnalyst identified two upregulated genes as the most crucial genes in the cerebellum of children with ASD: Jun proto-oncogene (JUN) and platelet-derived growth factor receptor alpha (PDGFRA). According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, genes associated with JUN in the cerebellum highlight the pathways of Th17 cell differentiation and Th1 and Th2 cell differentiation. Genes associated with PDGFRA in the cerebellum were enriched in the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance and Rap1 signalling pathways. The analysis of all the differentially expressed genes (DEGs) of the two datasets using gene set enrichment analysis (GSEA) demonstrated the involvement of the IL-17 signalling pathway, which is related to the expression of JUN and PDGFRA. ImmuCellAI found that elevated expression of JUN and PDGFRA correlated with the abundance of Th17 and monocytes, suggesting that JUN and PDGFRA could regulate Th17 cell activation and monocyte infiltration. Our ASD mouse model of maternal immune activation demonstrated that JUN and PDGFRA were upregulated in ASD mice. Limitations: The function of JUN and PDGFRA in patients of ASD and different ASD mouse models require explore and validation, and the results should be replicated in more patients with ASD. Conclusions: JUN and PDGFRA are crucial candidate genes and related to the IL-17 signalling pathway in ASD patients.

show abstract

Section: Discussionmentioning

confidence: 99%

“…However, studies on PDGFRA in ASD are limited. Numerous researchers have found that both adult and paediatric forms of glioblastoma (GBM) are related to the activation of PDGFRA [38] . Furthermore, EGFR kinase, the most prominent oncogenic target for GBM, has been disappointing after inhibited by drugs in clinical trials [45] .…”

Section: Discussionmentioning

confidence: 99%

JUN and PDGFRA as Crucial Candidate Genes for Childhood Autism Spectrum Disorder

Wang

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…PDGF group kinases are essential for tumor growth and ablation. It is associated with a higher grade of tumor burden in ER + BRCA [ 30 , 65 ]. Therefore, blockade of PDGF would be one of the most promising strategies to mitigate the invasion of BRCA.…”

Section: Recent Updates On Selective Tyrosine Kinase Inhibitors In Pre-clinical Studiesmentioning

confidence: 99%

Emerging Importance of Tyrosine Kinase Inhibitors against Cancer: Quo Vadis to Cure?

Mongre

Mishra

Shukla

et al. 2021

IJMS

View full text Add to dashboard Cite

GLOBOCAN 2020 estimated more than 19.3 million new cases, and about 10 million patients were deceased from cancer in 2020. Clinical manifestations showed that several growth factor receptors consisting of transmembrane and cytoplasmic tyrosine kinase (TK) domains play a vital role in cancer progression. Receptor tyrosine kinases (RTKs) are crucial intermediaries of the several cellular pathways and carcinogenesis that directly affect the prognosis and survival of higher tumor grade patients. Tyrosine kinase inhibitors (TKIs) are efficacious drugs for targeted therapy of various cancers. Therefore, RTKs have become a promising therapeutic target to cure cancer. A recent report shows that TKIs are vital mediators of signal transduction and cancer cell proliferation, angiogenesis, and apoptosis. In this review, we discuss the structure and function of RTKs to explore their prime role in cancer therapy. Various TKIs have been developed to date that contribute a lot to treating several types of cancer. These TKI based anticancer drug molecules are also discussed in detail, incorporating their therapeutic efficacy, mechanism of action, and side effects. Additionally, this article focuses on TKIs which are running in the clinical trial and pre-clinical studies. Further, to gain insight into the pathophysiological mechanism of TKIs, we also reviewed the impact of RTK resistance on TKI clinical drugs along with their mechanistic acquired resistance in different cancer types.

show abstract

“…The fate of this well-defined GIST population has recently changed with the advent of new drugs specifically directed to D842V mutations, such as crenolanib and especially avapritinib [14][15][16]. Furthermore, in recent years, the biological background of D842Vmutant GIST has been deeply investigated to better understand the molecular features of this peculiar subset of GIST, and some promising insights have emerged [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

The Identity of PDGFRA D842V-Mutant Gastrointestinal Stromal Tumors (GIST)

Rizzo

Pantaleo

Astolfi

et al. 2021

Cancers

View full text Add to dashboard Cite

The majority of gastrointestinal stromal tumors (GIST) carry a sensitive primary KIT mutation, but approximately 5% to 10% of cases harbor activating mutations of platelet-derived growth factor receptor (PDGFRA), mainly involving the A-loop encoded by exon 18 (~5%), or more rarely the JM domain, encoded by exon 12 (~1%), or the ATP binding domain encoded by exon 14 (<1%). The most frequent mutation is the substitution at position 842 in the A-loop of an aspartic acid (D) with a valine (V) in exon 18, widely recognized as D842V. This mutation, as well known, provides primary resistance to imatinib and sunitinib. Thus, until few years ago, no active drugs were available for this subtype of GIST. Conversely, recent years have witnessed the development of a new specific inhibitor—avapritinib—that has been studied in in vitro and clinical setting with promising results. In light of this primary resistance to conventional therapies, the biological background of D842V-mutant GIST has been deeply investigated to better understand what features characterize this peculiar subset of GIST, and some promising insights have emerged. Hereinafter, we present a comprehensive overview on the clinical features and the molecular background of this rare subtype of GIST.

show abstract

PDGF receptor mutations in human diseases

Cited by 69 publications

References 134 publications

JUN and PDGFRA as Crucial Candidate Genes for Childhood Autism Spectrum Disorder

JUN and PDGFRA as Crucial Candidate Genes for Childhood Autism Spectrum Disorder

Emerging Importance of Tyrosine Kinase Inhibitors against Cancer: Quo Vadis to Cure?

The Identity of PDGFRA D842V-Mutant Gastrointestinal Stromal Tumors (GIST)

Contact Info

Product

Resources

About