Genomes and Genes
Gene Symbol: PDGFR alpha
Description: platelet derived growth factor receptor alpha
Alias: CD140A, PDGFR-2, PDGFR2, platelet-derived growth factor receptor alpha, CD140 antigen-like family member A, CD140a antigen, PDGF-R-alpha, alpha-type platelet-derived growth factor receptor, platelet-derived growth factor receptor 2, platelet-derived growth factor receptor, alpha polypeptide
Products: PDGFR alpha
- Heldin C, Westermark B. Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev. 1999;79:1283-316 pubmed..This review discusses structural and functional properties of PDGF and PDGF receptors, the mechanism whereby PDGF exerts its cellular effects, and the role of PDGF in normal and diseased tissues...
- Nupponen N, Paulsson J, Jeibmann A, Wrede B, Tanner M, Wolff J, et al. Platelet-derived growth factor receptor expression and amplification in choroid plexus carcinomas. Mod Pathol. 2008;21:265-70 pubmed
- Sim F, McClain C, Schanz S, Protack T, Windrem M, Goldman S. CD140a identifies a population of highly myelinogenic, migration-competent and efficiently engrafting human oligodendrocyte progenitor cells. Nat Biotechnol. 2011;29:934-41 pubmed publisher..To establish a more efficient means of isolating myelinogenic OPCs, we sorted fetal human forebrain cells for CD140a, an epitope of platelet derived growth factor receptor (PDGFR)?, which is differentially expressed by OPCs...
- Miselli F, Casieri P, Negri T, Orsenigo M, Lagonigro M, Gronchi A, et al. c-Kit/PDGFRA gene status alterations possibly related to primary imatinib resistance in gastrointestinal stromal tumors. Clin Cancer Res. 2007;13:2369-77 pubmed..Our findings show that c-Kit/PDGFRA genomic alterations were present at disease onset in 1/3 of the examined cases. They therefore represent an early event possibly related to primary imatinib resistance in GISTs. ..
- Ball S, Shuttleworth C, Kielty C. Platelet-derived growth factor receptor-alpha is a key determinant of smooth muscle alpha-actin filaments in bone marrow-derived mesenchymal stem cells. Int J Biochem Cell Biol. 2007;39:379-91 pubmed..This study thus provides new insights into the distinct roles of platelet-derived growth factor receptor-alpha and -beta signaling in regulating the adult mesenchymal stem cell contractile cytoskeleton. ..
- Corless C, Schroeder A, Griffith D, Town A, McGreevey L, Harrell P, et al. PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J Clin Oncol. 2005;23:5357-64 pubmed..A subset of GISTs, however, contains mutations in the homologous kinase platelet derived growth factor receptor alpha (PDGFRA), and the most common of these mutations is resistant to imatinib in vitro...
- Velghe A, van Cauwenberghe S, Polyansky A, Chand D, Montano Almendras C, Charni S, et al. PDGFRA alterations in cancer: characterization of a gain-of-function V536E transmembrane mutant as well as loss-of-function and passenger mutations. Oncogene. 2014;33:2568-76 pubmed publisher..Our results also underline the importance of characterizing novel kinase alterations in cancer patients. ..
- Tejada M, Yu L, Dong J, Jung K, Meng G, Peale F, et al. Tumor-driven paracrine platelet-derived growth factor receptor alpha signaling is a key determinant of stromal cell recruitment in a model of human lung carcinoma. Clin Cancer Res. 2006;12:2676-88 pubmed..We propose that therapies targeting this stromal cell type may be effective in treating certain types of solid tumors. ..
- Zhu K, Pan Q, Zhang X, Kong L, Fan J, Dai Z, et al. MiR-146a enhances angiogenic activity of endothelial cells in hepatocellular carcinoma by promoting PDGFRA expression. Carcinogenesis. 2013;34:2071-9 pubmed publisher..These results suggest that miR-146a plays a key role in regulating the angiogenic activity of ECs in HCC through miR-146a-BRCA1-PDGFRA pathway. MiR-146a and PDGFRA may emerge as potential anti-angiogenic targets on ECs for HCC therapy. ..
- Reis R, Martins A, Ribeiro S, Basto D, Longatto Filho A, Schmitt F, et al. Molecular characterization of PDGFR-alpha/PDGF-A and c-KIT/SCF in gliosarcomas. Cell Oncol. 2005;27:319-26 pubmed..Nevertheless, the presence of a PDGFR-a/PDGFA and c-Kit/SCF autocrine/paracrine stimulation loop in a proportion of cases, supports the potential role of specific tyrosine kinase inhibitors in the treatment of gliosarcomas. ..
- Lasota J, Miettinen M. KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs). Semin Diagn Pathol. 2006;23:91-102 pubmed..Mutation genotyping is a tool in GIST diagnosis and in assessment of sensitivity to kinase inhibitors. This is a US government work. There are no restrictions on its use. ..
- Zong L, Chen P. Prognostic value of KIT/PDGFRA mutations in gastrointestinal stromal tumors: a meta-analysis. World J Surg Oncol. 2014;12:71 pubmed publisher..47 (95% CI, 0.25 to 0.90)). KIT mutations, compared with PDGFRA mutations and wild type, represent a poorer prognostic marker in high risk or malignant GISTs. ..
- Grover M, Bernard C, Pasricha P, Parkman H, Abell T, Nguyen L, et al. Platelet-derived growth factor receptor ? (PDGFR?)-expressing "fibroblast-like cells" in diabetic and idiopathic gastroparesis of humans. Neurogastroenterol Motil. 2012;24:844-52 pubmed publisher..In conclusion, PDGFR? identifies FLC in human gastric smooth muscle. FLC were not altered in distribution or overall numbers in gastroparesis. Additional studies are required to determine their role in human GI function. ..
- Martinho O, Longatto Filho A, Lambros M, Martins A, Pinheiro C, Silva A, et al. Expression, mutation and copy number analysis of platelet-derived growth factor receptor A (PDGFRA) and its ligand PDGFA in gliomas. Br J Cancer. 2009;101:973-82 pubmed publisher..Taken together, our results could provide in the future a molecular basis for PDGFRA-targeted therapies in gliomas. ..
- Burford A, Little S, Jury A, Popov S, Laxton R, Doey L, et al. Distinct phenotypic differences associated with differential amplification of receptor tyrosine kinase genes at 4q12 in glioblastoma. PLoS ONE. 2013;8:e71777 pubmed publisher..Thus we have identified differential patterns of gene amplification and expression of RTKs at the 4q12 locus to be associated with specific phenotypes which may reflect their distinct underlying mechanisms. ..
- Han S, Chen P, Fan Q, Khor C, Sim X, Tay W, et al. Association of variants in FRAP1 and PDGFRA with corneal curvature in Asian populations from Singapore. Hum Mol Genet. 2011;20:3693-8 pubmed publisher..This is the first genome-wide survey of CC variation and we have identified two implicated loci in three genetically diverse Asian populations, suggesting the presence of common genetic etiology across multiple populations. ..
- Patel S, Kneuertz P, Delgado M, Kooby D, Staley C, El Rayes B, et al. Clinically relevant biomarkers to select patients for targeted inhibitor therapy after resection of hepatocellular carcinoma. Ann Surg Oncol. 2011;18:3384-90 pubmed publisher..This finding may help to select patients who would benefit from targeted inhibitor therapy in the adjuvant setting. ..
- Walz C, Score J, Mix J, Cilloni D, Roche Lestienne C, Yeh R, et al. The molecular anatomy of the FIP1L1-PDGFRA fusion gene. Leukemia. 2009;23:271-8 pubmed publisher..The variability in the anatomy of the FIP1L1-PDGFRA fusion has important implications for strategies to detect the fusion at diagnosis or for monitoring response to treatment. ..
- Oseini A, Roberts L. PDGFRalpha: a new therapeutic target in the treatment of hepatocellular carcinoma?. Expert Opin Ther Targets. 2009;13:443-54 pubmed..Platelet derived growth factor receptor-alpha (PDGFR-alpha) is involved in tumor angiogenesis and maintenance of the tumor microenvironment and has been implicated in development and metastasis of HCC...
- Ozawa T, Brennan C, Wang L, Squatrito M, Sasayama T, Nakada M, et al. PDGFRA gene rearrangements are frequent genetic events in PDGFRA-amplified glioblastomas. Genes Dev. 2010;24:2205-18 pubmed publisher..These results suggest the possibility that these PDGFRA mutants behave as oncogenes in this subset of gliomas, and that the prevalence of such rearrangements may have been considerably underestimated. ..
- Zheng S, Huang K, Tao D, Pan Y. Gene mutations and prognostic factors analysis in extragastrointestinal stromal tumor of a Chinese three-center study. J Gastrointest Surg. 2011;15:675-81 pubmed publisher..From the molecular genetics aspect, EGISTs may be a special subtype of GISTs. The results also show that the combination of mitotic counts and Ki-67 LI may be useful for predicting the prognosis of EGISTs. ..
- Wehler T, Frerichs K, Graf C, Drescher D, Schimanski K, Biesterfeld S, et al. PDGFRalpha/beta expression correlates with the metastatic behavior of human colorectal cancer: a possible rationale for a molecular targeting strategy. Oncol Rep. 2008;19:697-704 pubmed..03). In summary, our results revealed that PDGFRalpha/beta expression significantly correlates with lymphatic dissemination and therefore encourages application of PDGFRalpha/beta RTK-inhibitors within a combination therapy. ..
- Floege J, Eitner F, Alpers C. A new look at platelet-derived growth factor in renal disease. J Am Soc Nephrol. 2008;19:12-23 pubmed..Accordingly, targeted intervention against the various PDGF isoforms offers a promising novel therapeutic approach to renal disease. ..
- Do I, Araujo E, Kalil R, Bacchini P, Bertoni F, Unni K, et al. Protein expression of KIT and gene mutation of c-kit and PDGFRs in Ewing sarcomas. Pathol Res Pract. 2007;203:127-34 pubmed..These findings imply other mechanisms for KIT activity and leave open the question of whether imatinib would be efficacious in the treatment of Ewing sarcoma. ..
- Snuderl M, Fazlollahi L, Le L, Nitta M, Zhelyazkova B, Davidson C, et al. Mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma. Cancer Cell. 2011;20:810-7 pubmed publisher..The stable coexistence of different clones within the same tumor will have important clinical implications for tumor resistance to targeted therapies. ..
- Chen H, Gu X, Liu Y, Wang J, Wirt S, Bottino R, et al. PDGF signalling controls age-dependent proliferation in pancreatic β-cells. Nature. 2011;478:349-55 pubmed publisher..The discovery of a conserved pathway controlling age-dependent β-cell proliferation indicates new strategies for β-cell expansion. ..
- Gogate N, Verma L, Zhou J, Milward E, Rusten R, O Connor M, et al. Plasticity in the adult human oligodendrocyte lineage. J Neurosci. 1994;14:4571-87 pubmed
- Szerlip N, Pedraza A, Chakravarty D, Azim M, McGuire J, Fang Y, et al. Intratumoral heterogeneity of receptor tyrosine kinases EGFR and PDGFRA amplification in glioblastoma defines subpopulations with distinct growth factor response. Proc Natl Acad Sci U S A. 2012;109:3041-6 pubmed publisher..This phenomenon is especially common among tumors with PDGFRA amplification: overall, 43% of PDGFRA-amplified GBM were found to have amplification of EGFR or the hepatocyte growth factor receptor gene (MET) as well. ..
- Thorarinsdottir H, Santi M, McCarter R, Rushing E, Cornelison R, Jales A, et al. Protein expression of platelet-derived growth factor receptor correlates with malignant histology and PTEN with survival in childhood gliomas. Clin Cancer Res. 2008;14:3386-94 pubmed publisher..to assess total expression of EGFR, PDGFR beta, and PTEN and expression of phosphorylated EGFR, phosphorylated PDGFR alpha (p-PDGFR alpha), phosphorylated AKT, phosphorylated mitogen-activated protein kinase, and phosphorylated ..
- Cools J, DeAngelo D, Gotlib J, Stover E, Legare R, Cortes J, et al. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med. 2003;348:1201-14 pubmed..The acquisition of a T674I resistance mutation at the time of relapse demonstrates that FIP1L1-PDGFRalpha is the target of imatinib. Our data indicate that the deletion of genetic material may result in gain-of-function fusion proteins. ..
- Subramanian S, West R, Corless C, Ou W, Rubin B, Chu K, et al. Gastrointestinal stromal tumors (GISTs) with KIT and PDGFRA mutations have distinct gene expression profiles. Oncogene. 2004;23:7780-90 pubmed..These gene products could serve as highly selective therapeutic targets in GISTs containing the KIT or PDGFRA mutational types with which they are associated. ..
- Cools J, Quentmeier H, Huntly B, Marynen P, Griffin J, Drexler H, et al. The EOL-1 cell line as an in vitro model for the study of FIP1L1-PDGFRA-positive chronic eosinophilic leukemia. Blood. 2004;103:2802-5 pubmed
- Paugh B, Qu C, Jones C, Liu Z, Adamowicz Brice M, Zhang J, et al. Integrated molecular genetic profiling of pediatric high-grade gliomas reveals key differences with the adult disease. J Clin Oncol. 2010;28:3061-8 pubmed publisher..PDGFRalpha may be a useful target for pediatric HGG, including diffuse pontine gliomas. ..
- Liu K, Feng H, Bachoo R, Kazlauskas A, Smith E, Symes K, et al. SHP-2/PTPN11 mediates gliomagenesis driven by PDGFRA and INK4A/ARF aberrations in mice and humans. J Clin Invest. 2011;121:905-17 pubmed publisher..These findings functionally validate the genomic analysis of glioblastomas and identify SHP-2 as a potential target for treatment of glioblastomas. ..
- Andersson J, Bümming P, Meis Kindblom J, Sihto H, Nupponen N, Joensuu H, et al. Gastrointestinal stromal tumors with KIT exon 11 deletions are associated with poor prognosis. Gastroenterology. 2006;130:1573-81 pubmed..KIT exon 11 duplications and exon 9 mutations were found exclusively in gastric and small intestinal GIST, respectively. KIT exon 11 deletion is an independent adverse prognostic factor in patients with GIST. ..
- Debiec Rychter M, Cools J, Dumez H, Sciot R, Stul M, Mentens N, et al. Mechanisms of resistance to imatinib mesylate in gastrointestinal stromal tumors and activity of the PKC412 inhibitor against imatinib-resistant mutants. Gastroenterology. 2005;128:270-9 pubmed..In a subset of patients, cancer cells lost their dependence on the targeted tyrosine kinase. Our findings show the sensitivity of the imatinib-resistant KIT -T670I and KIT -V654A and of PDGFRA -D842V mutants to PKC412. ..
- Gomes A, Gouveia A, Capelinha A, de la Cruz D, Silva P, Reis R, et al. Molecular alterations of KIT and PDGFRA in GISTs: evaluation of a Portuguese series. J Clin Pathol. 2008;61:203-8 pubmed..The great majority of mutations were located in KIT exon 11, statistically associated with worse prognosis and indicative of favourable response to imatinib-based therapy in this Portuguese series of GISTs. ..
- Verhaak R, Hoadley K, Purdom E, Wang V, Qi Y, Wilkerson M, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010;17:98-110 pubmed publisher..We provide a framework that unifies transcriptomic and genomic dimensions for GBM molecular stratification with important implications for future studies. ..
- Maleddu A, Pantaleo M, Nannini M, Biasco G. The role of mutational analysis of KIT and PDGFRA in gastrointestinal stromal tumors in a clinical setting. J Transl Med. 2011;9:75 pubmed publisher..Patients with GIST harboring a PDGFRA mutation seem to have a better prognosis than the others.The aim of this paper is to review the clinical significance of tyrosine kinase mutational status. ..
- Phillips J, Huillard E, Robinson A, Ward A, Lum D, Polley M, et al. Heparan sulfate sulfatase SULF2 regulates PDGFR? signaling and growth in human and mouse malignant glioma. J Clin Invest. 2012;122:911-22 pubmed publisher..Our results suggest the bioavailability of growth factors from the microenvironment is a significant contributor to tumor growth in a major subset of human GBM. ..
- Zietsch J, Ziegenhagen N, Heppner F, Reuss D, von Deimling A, Holtkamp N. The 4q12 amplicon in malignant peripheral nerve sheath tumors: consequences on gene expression and implications for sunitinib treatment. PLoS ONE. 2010;5:e11858 pubmed publisher..Sunitinib is a drug targeting receptor tyrosine kinases (RTK) like PDGFRalpha, c-Kit and VEGFR-2. These genes are structurally related and cluster on chromosomal segment 4q12...
- Mishra A, Yazar S, Hewitt A, Mountain J, Ang W, Pennell C, et al. Genetic variants near PDGFRA are associated with corneal curvature in Australians. Invest Ophthalmol Vis Sci. 2012;53:7131-6 pubmed publisher..Results of initial genomewide association studies (GWAS) for CC in Australians were also reported...
- Braconi C, Bracci R, Bearzi I, Bianchi F, Costagliola A, Catalani R, et al. KIT and PDGFRalpha mutations in 104 patients with gastrointestinal stromal tumors (GISTs): a population-based study. Ann Oncol. 2008;19:706-10 pubmed publisher..Point mutations and duplications in KIT exon 11 are associated with a better clinical trend in DFS. PDGFRalpha-mutated GISTs are preferentially localized in the stomach and seem to have a favorable clinical behavior. ..
- Tzen C, Wang M, Mau B. Spectrum and prognostication of KIT and PDGFRA mutation in gastrointestinal stromal tumors. Eur J Surg Oncol. 2008;34:563-8 pubmed
- Kim Y, Kim E, Wu Q, Guryanova O, Hitomi M, Lathia J, et al. Platelet-derived growth factor receptors differentially inform intertumoral and intratumoral heterogeneity. Genes Dev. 2012;26:1247-62 pubmed publisher..Our results may explain mixed clinical responses of anti-PDGFR-based approaches and suggest the need for integration of models of cancer as an organ system into development of cancer therapies. ..
- Chen D, Persson A, Sun Y, Salford L, Nord D, Englund E, et al. Better prognosis of patients with glioma expressing FGF2-dependent PDGFRA irrespective of morphological diagnosis. PLoS ONE. 2013;8:e61556 pubmed publisherSignaling of platelet derived growth factor receptor alpha (PDGFRA) is critically involved in the development of gliomas...
- Trojani A, Ripamonti C, Penco S, Beghini A, Nadali G, Di Bona E, et al. Molecular analysis of PDGFRA and PDGFRB genes by rapid single-strand conformation polymorphism (SSCP) in patients with core-binding factor leukaemias with KIT or FLT3 mutation. Anticancer Res. 2008;28:2745-51 pubmed..Thus, PDGFR genes do not seem to be involved in CBFL and future studies are needed to establish the genetic causes of the disease in these particular patients. ..
- Eckert M, Lwin T, Chang A, Kim J, Danis E, Ohno Machado L, et al. Twist1-induced invadopodia formation promotes tumor metastasis. Cancer Cell. 2011;19:372-86 pubmed publisher..Therefore, invadopodia-mediated matrix degradation is a key function of Twist1 in promoting tumor metastasis...
- Schimanski C, Zimmermann T, Schmidtmann I, Gockel I, Lang H, Galle P, et al. K-ras mutation status correlates with the expression of VEGFR1, VEGFR2, and PDGFRalpha in colorectal cancer. Int J Colorectal Dis. 2010;25:181-6 pubmed publisher..0145). Our data reveal that specific RTKs are over-expressed in K-ras mutated cancers. It needs to be addressed in prospective studies whether these patients will benefit from tyrosine kinase inhibitors more than K-ras wild-type. ..
- Cho S, Kitadai Y, Yoshida S, Tanaka S, Yoshihara M, Yoshida K, et al. Deletion of the KIT gene is associated with liver metastasis and poor prognosis in patients with gastrointestinal stromal tumor in the stomach. Int J Oncol. 2006;28:1361-7 pubmed..Our data indicate that KIT mutations, especially deletions in exon 11, are markers of poor prognosis for gastric GISTs. ..
- Holtkamp N, Okuducu A, Mucha J, Afanasieva A, Hartmann C, Atallah I, et al. Mutation and expression of PDGFRA and KIT in malignant peripheral nerve sheath tumors, and its implications for imatinib sensitivity. Carcinogenesis. 2006;27:664-71 pubmed..In summary, PDGFRA, PDGF and KIT dysregulation as well as growth inhibition of cell culture S462 by imatinib may suggest that MPNST patients benefit from treatment with imatinib. ..
- Rand V, Huang J, Stockwell T, Ferriera S, Buzko O, Levy S, et al. Sequence survey of receptor tyrosine kinases reveals mutations in glioblastomas. Proc Natl Acad Sci U S A. 2005;102:14344-9 pubmed..Our results demonstrate the utility of applying DNA sequencing technology to systematically assess the coding sequence of genes within cancer genomes. ..
- Carvalho I, Milanezi F, Martins A, Reis R, Schmitt F. Overexpression of platelet-derived growth factor receptor alpha in breast cancer is associated with tumour progression. Breast Cancer Res. 2005;7:R788-95 pubmed
- Heinrich M, Corless C, Duensing A, McGreevey L, Chen C, Joseph N, et al. PDGFRA activating mutations in gastrointestinal stromal tumors. Science. 2003;299:708-10 pubmed..Thus, KIT and PDGFRA mutations appear to be alternative and mutually exclusive oncogenic mechanisms in GISTs. ..
- Pinzani M, Milani S, Herbst H, DeFranco R, Grappone C, Gentilini A, et al. Expression of platelet-derived growth factor and its receptors in normal human liver and during active hepatic fibrogenesis. Am J Pathol. 1996;148:785-800 pubmed
- Agaram N, Wong G, Guo T, Maki R, Singer S, Dematteo R, et al. Novel V600E BRAF mutations in imatinib-naive and imatinib-resistant gastrointestinal stromal tumors. Genes Chromosomes Cancer. 2008;47:853-9 pubmed publisher..A secondary V600E BRAF mutation could represent an alternative mechanism of imatinib resistance. Kinase inhibitors targeting BRAF may be effective therapeutic options in this molecular GIST subset. ..
- Lasota J, Miettinen M. Clinical significance of oncogenic KIT and PDGFRA mutations in gastrointestinal stromal tumours. Histopathology. 2008;53:245-66 pubmed publisher..GISTs with secondary mutations in exon 13 and 14 are sensitive to sunitinib, another tyrosine kinase inhibitor. KIT and PDGFRA genotyping is important for GIST diagnosis and assessment of sensitivity to tyrosine kinase inhibitors. ..
- Ribom D, Andrae J, Frielingsdorf M, Hartman M, Nister M, Smits A. Prognostic value of platelet derived growth factor alpha receptor expression in grade 2 astrocytomas and oligoastrocytomas. J Neurol Neurosurg Psychiatry. 2002;72:782-7 pubmed..The findings suggest that expression of the receptor may be a useful prognostic marker in such patients. ..
- Demoulin J, Essaghir A. PDGF receptor signaling networks in normal and cancer cells. Cytokine Growth Factor Rev. 2014;25:273-83 pubmed publisher..Of particular interest, recent studies revealed significant differences between normal and cancer cells regarding signal transduction by these growth factors. ..