ライフサイエンスコーパス: PDGFRA

1 PDGFRA amplification and 1q gain occurred at significant

2 PDGFRA intragenic deletion of exons 8 and 9 were previou

3 PDGFRA mutations and KIT exon 11 insertion or duplicatio

4 PDGFRA was the predominant target of focal amplification

5 PDGFRA(hi) telocytes are especially abundant at the vill

6 PDGFRA, a receptor whose activity is required for cell m

7 PDGFRA-mutant GISTs expressed many chemokines, such as C

8 PDGFRA/NG2 cells generated very few GFAP(+)-reactive ast

9 FIP1L1-PDGFRA-myeloid neoplasm (FP; n =12), PDGFRA-negative HES with >/=4 criteria suggestive of a m

10 4 astrocytomas and included the MDM4 (1q32), PDGFRA (4q12), MET (7q21), CMYC (8q24), PVT1 (8q24), WNT

11 tation, 43 (12.6%) had GISTs that harbored a PDGFRA mutation, and 24 (7.0%) had GISTs that were wild

12 tinal stromal tumour, and 36 patients with a PDGFRA D842V-mutant gastrointestinal stromal tumour were

13 scalation part, including 20 patients with a PDGFRA D842V-mutant gastrointestinal stromal tumour, and

14 er KIT or platelet-derived growth factor A ( PDGFRA).

15 the KIT or platelet-derived growth factor A (PDGFRA) gene.

16 her KIT or platelet-derived growth factor A (PDGFRA).

17 r platelet-derived growth factor receptor A (PDGFRA) mutations respond to treatment with targeted KIT

18 e platelet-derived growth factor receptor A (PDGFRA), as well as novel RNA-binding protein interactor

19 nd absence of the molecular lesions BCR/ABL, PDGFRA, PDGFRB, and FGFR1.

20 either wild-type or constitutively activated PDGFRA (platelet-derived growth factor receptor-alpha) u

21 ding of rearranged, constitutively activated PDGFRA/B identifies patients who are eminently treatable

22 0% of G34R/V tumors (n = 95) bear activating PDGFRA mutations that display strong selection pressure

23 e kinase receptors, including ACVR1, ACVR2B, PDGFRA, TGFBR1, and TGFBR3.

24 ntitumour activity in patients with advanced PDGFRA D842V-mutant gastrointestinal stromal tumours.

25 ed by copy number analysis, we sequenced all PDGFRA coding exons from a cohort of pediatric HGGs.

26 KIT or platelet-derived growth factor alpha (PDGFRA) kinases, which are targets for imatinib.

27 IT and platelet-derived growth factor-alpha (PDGFRA), which is commonly seen in this tumor.

28 atelet-derived growth factor receptor alpha (PDGFRA) (F/P) fusion gene has been identified as a cause

29 atelet-derived growth factor receptor alpha (PDGFRA) amplification.

30 atelet-derived growth factor receptor alpha (PDGFRA) and epidermal growth factor receptor (EGFR).

31 atelet derived growth factor receptor alpha (PDGFRA) and type 3 fibroblast growth factor receptor (FG

32 atelet derived growth factor receptor alpha (PDGFRA) antibodies have been associated with extensive c

33 at either IGF-1R or the PDGF receptor alpha (PDGFRA) can mediate intrinsic resistance to rapamycin.

34 atelet-derived growth factor receptor alpha (PDGFRA) genes.

35 atelet-derived growth factor receptor alpha (PDGFRA) have been reported in a subset of gastrointestin

36 atelet-derived growth factor receptor alpha (PDGFRA) in prostate cells and indirectly influences the

37 atelet-derived growth factor receptor alpha (PDGFRA) is a clinical challenge for patients with advanc

38 atelet-derived growth factor receptor alpha (PDGFRA) is the most frequent target of focal amplificati

39 atelet-derived growth factor receptor alpha (PDGFRA) kinases, which are imatinib targets.

40 atelet-derived growth factor receptor alpha (PDGFRA) mutations in contrast to a mutation rate of 80%

41 atelet-derived growth factor receptor alpha (PDGFRA) mutations.

42 atelet-derived growth factor receptor alpha (PDGFRA) overexpression is concomitant with a loss of cyc

43 atelet-derived growth factor receptor alpha (PDGFRA) receptor tyrosine kinase proteins, and these kin

44 atelet-derived growth factor receptor alpha (PDGFRA) to be the receptor for PC-independent infection

45 atelet-derived growth factor receptor alpha (PDGFRA) tyrosine kinases.

46 atelet-derived growth factor receptor alpha (PDGFRA), and fibroblast growth factor receptor 1 (FGFR1)

47 atelet derived growth factor receptor alpha (PDGFRA), and the most common of these mutations is resis

48 atelet-derived growth factor receptor-alpha (PDGFRA) gene rearrangement in these tumors is unknown.

49 atelet-derived growth factor receptor-alpha (PDGFRA), as evident from the expression of myogenic mark

50 latelet-derived growth factor receptor alpha(PDGFRA), which can be therapeutically targeted by tyrosi

51 Instead, an PDGFRA(HI)/F3(HI)/DLL1(HI) mesenchymal population lines

52 One of five oncogenes analyzed (PDGFRA) was amplified in one patient.

53 rongly influenced by the balance of EGFR and PDGFRA activation in individual cells, which is heteroge

54 was performed on eight samples with EGFR and PDGFRA amplification, revealing distinct tumor cell subp

55 K activation levels correlated with EGFR and PDGFRA expression, and p-FAK and EGFR expression co-loca

56 Concurrent amplifications of EGFR and PDGFRA have been reported in up to 5% of glioblastoma (G

57 Here, we document that EGFR and PDGFRA protein co-expression occurs in 37% of GBM.

58 most commonly amplified RTK genes, EGFR and PDGFRA, were found to be present in variable proportions

59 s of signature receptors, including EGFR and PDGFRA.

60 number amplifications of the CDK4, EGFR, and PDGFRA loci and by mutations in the NF1 locus, which eac

61 ted with the mTORC1 inhibitor everolimus and PDGFRA inhibitor imatinib mesylate confirmed that this d

62 expressed minimal to null levels of KIT and PDGFRA but expressed levels of PDGFRB that are comparabl

63 mal tumours, including patients with KIT and PDGFRA D842V-mutant gastrointestinal stromal tumours (NA

64 l stromal tumors (GISTs), which lack KIT and PDGFRA gene mutations, are the primary form of GIST in c

65 racteristic somatic mutations in the KIT and PDGFRA genes in GIST tumors may similarly be mutational

66 our activity of avapritinib, a novel KIT and PDGFRA inhibitor that potently inhibits PDGFRA D842V, in

67 inhibit the full spectrum of mutant KIT and PDGFRA kinases found in cancers and myeloproliferative n

68 a well-tolerated, novel inhibitor of KIT and PDGFRA mutant kinases with promising activity in patient

69 Ripretinib inhibits all tested KIT and PDGFRA mutants, and notably is a type II kinase inhibito

70 KIT and PDGFRA mutation analysis was done in 27 pediatric GISTs.

71 KIT and PDGFRA mutations account for 85-90% of GISTs; subsequent

72 To investigate the effect of KIT and PDGFRA mutations on recurrence-free survival (RFS) in pa

73 nt of GIST harboring the most common KIT and PDGFRA mutations, optimal management of other genotypic

74 r active against a broad spectrum of KIT and PDGFRA mutations, with placebo in patients with previous

75 designed to inhibit a wide range of KIT and PDGFRA mutations.

76 tation or patients with GIST lacking KIT and PDGFRA mutations.

77 zed GISTs with mutation analysis for KIT and PDGFRA performed centrally using conventional sequencing

78 Mutational analysis of KIT and PDGFRA should ideally be performed in all patients with

79 echanisms of genetic progression and KIT and PDGFRA transforming roles in pediatric GIST might facili

80 ific for EGFR and GIST patients with KIT and PDGFRA tyrosine kinase inhibitors.

81 Targeting of KIT and PDGFRA with imatinib revolutionised treatment in gastroi

82 inhibit activation loop mutations in KIT and PDGFRA, previously thought only achievable with type I i

83 erences in the immune infiltrates of KIT and PDGFRA-mutant GIST.

84 profiles capable of differentiating KIT and PDGFRA-mutant GISTs, and also identified additional immu

85 other HSP90 client proteins, beyond KIT and PDGFRA.

86 given imatinib, a drug that targets KIT and PDGFRA.

87 atment, and the mutational status of KIT and PDGFRA.

88 he related receptor tyrosine kinases KIT and PDGFRA.

89 K27M expression synergizes with p53 loss and PDGFRA activation in neural progenitor cells derived fro

90 predicted target genes (BMP2, FGF9, PAX9 and PDGFRA).

91 Anti-PDGFRA antibodies were observed in 7 of 11 evaluable sub

92 ng caused by overexpression of genes such as PDGFRA is responsible for robust glioma growth and cell

93 as well as in chronic myeloid leukemia (BCR-PDGFRA translocation), and sunitinib can yield clinical

94 MMP3 produced by PDGFRA(+) fibroblasts is important for serrated polyp de

95 a BMP reservoir, and we identified a CD81(+) PDGFRA(lo) population present just below crypts that sec

96 Subsets of cecal PDGFRA(+) fibroblasts are activated by release of IL1B f

97 Genes (CAPZB, COL9A2, PDGFRA, MAP3K5, ZNF410, and PKM2) involved in muscle str

98 o-option through a chromatin loop connecting PDGFRA to GSX2 regulatory elements, promoting PDGFRA ove

99 acted in a cooperative fashion against D842V-PDGFRA.

100 significantly less efficacious against D842V-PDGFRA.

101 potential of nilotinib monotherapy for D842V-PDGFRA-associated GIST.

102 T, although the reduced sensitivity of D842V-PDGFRA probably limits the potential of nilotinib monoth

103 ation studies performed with V561D- or D842V-PDGFRA mutants.

104 e V561D-PDGFRA mutant in vitro and the D842V-PDGFRA mutant in vitro and in vivo.

105 ng skeletal muscle defects, the hESC-derived PDGFRA(+) cells exhibit significant in vitro expansion w

106 uencing (RNA-seq) to identify three distinct PDGFRA(+) mesenchymal cell types.

107 estores insulator function and downregulates PDGFRA.

108 , and hallmark copy number variations (EGFR, PDGFRA, MDM4, and CDK4 amplification; PTEN, CDKN2A, NF1,

109 on, integrin expression was enriched in EGFR/PDGFRA-overexpressing areas but was more regionally conf

110 The lineage of origin may facilitate PDGFRA co-option through a chromatin loop connecting PDG

111 we detected mutations in ERBB2, EGFR, FGFR1, PDGFRA, and MAP2K1 as potential mechanisms of primary re

112 oid-sparing for patients negative for FIP1L1-PDGFRA who have the hypereosinophilic syndrome.

113 Eligible patients had FIP1L1-PDGFRA-negative HES, experienced 2 or more flares (worse

114 chieved at least a 3-log reduction in FIP1L1-PDGFRA fusion transcripts relative to the pretreatment l

115 tinib was followed by a rapid rise in FIP1L1-PDGFRA transcript levels.

116 Normalized FIP1L1-PDGFRA transcript levels in patient samples prior to ima

117 In 2003, a karyotypically-occult FIP1L1-PDGFRA was reported in a subset of patients with blood e

118 aken in patients with a high level of FIP1L1-PDGFRA expression prior to initiation of imatinib (100 m

119 lts were not affected by exclusion of FIP1L1-PDGFRA-positive cases.

120 one marrow and blood samples revealed FIP1L1-PDGFRA-positive chronic eosinophilic leukemia.

121 Patients were negative for the FIP1L1-PDGFRA fusion gene and required prednisone monotherapy,

122 The FIP1L1-PDGFRA fusion gene is a recurrent molecular lesion in eo

123 the exception of the presence of the FIP1L1-PDGFRA fusion gene, little is known about predictors of

124 The FIP1L1-PDGFRA fusion transcript was detected at a sensitivity o

125 Subjects with FIP1L1-PDGFRA-myeloid neoplasm (FP; n =12), PDGFRA-negative HES

126 of a patient with GEH associated with FIP1L1-PDGFRA-positive chronic eosinophilic leukemia.

127 s clearly the treatment of choice for FIP1L1/PDGFRA-positive chronic eosinophilic leukemia (CEL), lit

128 imination of the clonal population in FIP1L1/PDGFRA-positive CEL and suggest that molecular monitorin

129 le-blind, placebo-controlled study of FIP1L1/PDGFRA-negative, corticosteroid-responsive subjects with

130 In a subset of these patients, the FIP1L1/PDGFRA (F/P) oncoprotein is detectable.

131 ress these questions, 5 patients with FIP1L1/PDGFRA-positive CEL with documented clinical, hematologi

132 receptors despite increased mRNA levels for PDGFRA.

133 onsensus regulatory loop (miR17/miR20a-FOXE1-PDGFRA) and eight miRNAs (miR-140, miR-17, miR-18a, miR-

134 Lu et al. describe a phenotypic switch from PDGFRA-enriched "proneural" to EGFR-enriched "classical"

135 differentially expressed in PDX tumors, e.g. PDGFRA, PDGFRB and CSF1R.

136 antly with the receptor tyrosine kinase gene PDGFRA, a prominent glioma oncogene.

137 r placebo in 20 symptomatic patients who had PDGFRA-negative hypereosinophilic syndrome and an absolu

138 high-grade gliomas (HGGs) frequently harbor PDGFRA alterations.

139 in gastrointestinal stromal tumour; however, PDGFRA Asp842Val (D842V)-mutated gastrointestinal stroma

140 Re-introducing human PDGFRA gene into knockout cells restored susceptibility

141 survivin, TOP2A, LYVE1, E-cadherin, IGFBP3, PDGFRA, TGFA, cyclin D1, and HGF.

142 Importantly, PDGFRA was absent in epithelial and trophoblast cells, w

143 B/p14ARF as early events, and aberrations in PDGFRA and PTEN as later events during cancer progressio

144 a long-term corticosteroid-sparing agent in PDGFRA-negative HES.

145 K27M mutations and recurrent alterations in PDGFRA and TP53.

146 llow fluorescent protein (YFP) expression in PDGFRA/NG2 cells and their differentiated progeny.

147 We investigated the PDGFRA locus in PDGFRA-amplified gliomas and identified two rearrangemen

148 eatures of MHES predict imatinib response in PDGFRA-negative HES.

149 b through multiple pathways that may include PDGFRA signal transduction.

150 ented by additional RAS activators including PDGFRA.

151 Pre-clinically, this antibody inhibited PDGFRA-dependent tumor growth.

152 and PDGFRA inhibitor that potently inhibits PDGFRA D842V, in patients with advanced gastrointestinal

153 of DIPGs, the most common of which involved PDGFRA and MET.

154 KIT, PDGFRA, NF1 and SDH mutations are alternate initiating e

155 Tumor expression of total and activated KIT, PDGFRA, and PDGFRB were assessed using immunohistochemis

156 tive investigational inhibitor of FLT3, KIT, PDGFRA, PDGFRB and RET; evolution of AC220-resistant sub

157 other oncogenic kinases (BCR-ABL, HER2, KIT, PDGFRA, BRAF).

158 The activation status of KIT, PDGFRA, and downstream signaling intermediates was defin

159 No mutations of KIT, PDGFRA, or PDGFRB were found.

160 pecimens were analyzed for mutations of KIT, PDGFRA, PDGFRB, and CTNNB1 (beta-catenin).

161 KIT/PDGFRA mutational status was determined for 78 patients

162 RA-mutant GIST, similar progress against KIT/PDGFRA wild-type GIST, including mutant BRAF-driven tumo

163 ansporter type 4 (GLUT4) expression, and KIT/PDGFRA mutation status in patients with gastrointestinal

164 ies of 20 cases originally classified as KIT/PDGFRA wild-type GIST revealed that 17 (85.0%) harbored

165 We assessed the relationship between KIT/PDGFRA mutations and select deletions or single nucleoti

166 argeting is expected to be selective for KIT/PDGFRA and a subset of other HSP90 clients, and thereby

167 ing strategy for inactivating the myriad KIT/PDGFRA oncoproteins in TKI-resistant GIST patients.

168 te clinical advances in the treatment of KIT/PDGFRA-mutant GIST, similar progress against KIT/PDGFRA

169 linical resistance to imatinib and other KIT/PDGFRA kinase inhibitors and there is an urgent need to

170 ry and secondary mutations of pathogenic KIT/PDGFRA oncoproteins.

171 tions respond to treatment with targeted KIT/PDGFRA inhibitors such as imatinib mesylate, these treat

172 testinal stromal tumors (GISTs), and the KIT/PDGFRA kinase inhibitor, imatinib, is standard of care f

173 consolidate GIST therapeutic response to KIT/PDGFRA inhibition.

174 ning mutations that confer resistance to KIT/PDGFRA kinase inhibitors.Oncogene advance online publica

175 (58%), KIT exon 11 (34%), and wild-type KIT/PDGFRA (56%).

176 The mechanistic events by which KIT/PDGFRA kinase inhibition leads to clinical responses in

177 nib-sensitive adenosquamous NSCLC cell line, PDGFRA expression was associated with focal PFGRA gene a

178 ly in a human FASD genome-wide dataset links PDGFRA to craniofacial phenotypes in FASD, prompting a m

179 T oncoproteins, suggesting that KIT-mediated PDGFRA phosphorylation is an efficient and biologically

180 tumors, rare tumors that show PDGFC-mediated PDGFRA activation may also be clinically responsive to p

181 al testing of PKC412 for treatment of mutant PDGFRA-GIST.

182 The responsiveness of mutant PDGFRA-positive GIST to imatinib depends on the location

183 expressing both the wild-type and the mutant PDGFRA transgenes in cells of neural crest origin.

184 in promoting transformation than the mutant PDGFRA, which is important because 78% of human MPNSTs h

185 in promoting transformation than the mutant PDGFRA, which is important because ~78% of human MPNSTs

186 PPK tumor-bearing mice (mutant TP53, mutant PDGFRA, H3K27M).

187 cers, and chromosome topology in KIT-mutant, PDGFRA-mutant and SDH-deficient GISTs.

188 nsable for tumor maintenance, whereas mutant-PDGFRA is potently oncogenic.

189 tion or point mutation, KIT exon 9 mutation, PDGFRA mutation, or wild-type tumor, although some of th

190 luding BLNK, DGKH, FGFR1, IL2RB, LYN, NTRK3, PDGFRA, PTK2B, TYK2, and the RAS signaling pathway.

191 s with PDGFRA amplification: overall, 43% of PDGFRA-amplified GBM were found to have amplification of

192 lasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1') and undefined (chronic eosino

193 b and test the hypothesis that abrogation of PDGFRA signaling can ameliorate the manifestations of cG

194 In contrast to KIT, activation of PDGFRA increased anchorage-independent proliferation and

195 d binding and thereby inhibits activation of PDGFRA kinase activity.

196 GFRII) and the PDGFRA gene, and six cases of PDGFRA(Delta8, 9), an intragenic deletion rearrangement.

197 The discovery of PDGFRA, PDGFRB, FGFR1, JAK-2, and FLT3 fusion proteins i

198 antibody against the extracellular domain of PDGFRA.

199 ression of HOXC6 can overcome the effects of PDGFRA inhibition.

200 Repressing expression of PDGFRA or inhibiting its kinase activity in synovial sar

201 To test this we examined the fates of PDGFRA/NG2 cells in the mouse spinal cord during experim

202 The natural history of PDGFRA- and PDGFRB-rearranged neoplasms has been dramati

203 We further show that inhibition of PDGFRA reduces proliferation of prostate cancer cells, a

204 lupus nephritis, intra-renal mRNA levels of PDGFRA and associated pathway members showed significant

205 We observed that loss of PDGFRA function in both organisms causes TAPVR with low

206 lasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK2" In addition

207 of dysplasia, BCR-ABL1 or rearrangements of PDGFRA, PDGFRB or FGFR1.

208 d evidence for functional transactivation of PDGFRA by EGFR and EGF-induced receptor heterodimerizati

209 Little is known of the other types of PDGFRA mutations that occur in GISTs.

210 Tumors with these two types of PDGFRA rearrangement displayed histologic features of ol

211 ion formation and results in upregulation of PDGFRA expression.

212 nd human primary HGG cells with a variety of PDGFRA alterations.

213 A similar codependency on PDGFRA and PDGFC was observed in the sunitinib-sensitive

214 ouse models driven by mutated RTK oncogenes, PDGFRA and NTRK1, analyzing 13,860 proteins and 30,431 p

215 tivating mutations in either KIT (75-80%) or PDGFRA (5-10%), two closely related receptor tyrosine ki

216 occurred in regions of elevated EGFR and/or PDGFRA expression.

217 in sporadic GIST lacking mutations in KIT or PDGFRA (WT).

218 have somatic mutations in either the KIT or PDGFRA gene, but there are no known inherited genetic ri

219 stinal stromal tumors (GISTs) contain KIT or PDGFRA kinase gain-of-function mutations, and therefore

220 KIT or PDGFRA mutation was detected in 333 of 366 tumors (91%)

221 and the oncogenic driver is usually a KIT or PDGFRA mutation.

222 is activated in GIST, irrespective of KIT or PDGFRA mutational status, and is expressed at levels unp

223 or amplifications; and sunitinib for KIT or PDGFRA mutations or amplification.

224 l stromal tumors (WT-GISTs) that lack KIT or PDGFRA mutations represent a unique subtype of GIST that

225 Oncogenic KIT or PDGFRA receptor tyrosine kinase mutations are compelling

226 efined by activating mutations in the KIT or PDGFRA receptor tyrosine kinases.

227 Secondary kinase mutations of KIT or PDGFRA that were identified in imatinib-resistant GISTs

228 Oncogenic KIT or PDGFRA tyrosine kinase mutations are compelling therapeu

229 Mutations in KIT or PDGFRA were identified in 11% of pediatric GISTs.

230 ations of the genes encoding the RTK KIT (or PDGFRA in a minority of cases) result in constitutive ki

231 r with known WT GIST (no mutations in KIT or PDGFRA) were recruited; 116 patients with WT GIST were e

232 mediated by constitutively activated KIT or PDGFRA.

233 -option of a potentially targetable pathway, PDGFRA signaling.

234 so be clinically responsive to pharmacologic PDGFRA or PDGFC inhibition.

235 Of 4 subjects with phospho-PDGFRA and phospho-PDGFRB immunohistochemistry studies b

236 ] showed expression of highly phosphorylated PDGFRA.

237 Notably, tyrosine-phosphorylated PDGFRA was prominent in frozen GIST tumors expressing KI

238 ies of the PDGF receptor, alpha polypeptide (PDGFRA) isoforms (V561D; D842V and delta842-845) carryin

239 DGFRA to GSX2 regulatory elements, promoting PDGFRA overexpression and mutation.

240 and subtype implementation, including PTEN, PDGFRA, RB1, VEGFA, STAT3, and RUNX1, suggesting that th

241 and included markers localized to 4q11-q13 (PDGFRA, GSX2; P=4.5x10(-7)), 16p12 (SLC5A11; P=5.1x10(-7

242 atelet-derived growth factor alpha receptor (PDGFRA)/NG2-expressing glia are distributed throughout t

243 (HCMV), GPCMV uses a specific cell receptor (PDGFRA) for fibroblast entry, but other receptors are re

244 eoplasm (MHES; n =10), or steroid-refractory PDGFRA-negative HES with <4 myeloid criteria (SR; n = 5)

245 d nilotinib, and imatinib, on 2 GIST-related PDGFRA mutants, V561D and D842V, which possess different

246 Including our cases, there are 289 reported PDGFRA-mutant GISTs, of which 181 (62.6%) had the imatin

247 Transient expression of representative PDGFRA isoforms in CHO cells revealed imatinib sensitivi

248 correlation between the expression of SDF1, PDGFRA, and PDGFRB, which is upregulated, along CXCR4 in

249 igand PDGFC was also detected, and silencing PDGFRA or PDGFC expression by RNA interference inhibited

250 Through generation of hepatocyte-specific PDGFRA knockout (KO) mice that lack an overt phenotype,

251 erived growth factor receptor alpha subunit (PDGFRA) and the NG2 proteoglycan.

252 COL3A1, COL5A1, POSTN, CTGF, LOX, TGFbeta1, PDGFRA, TNC, BGN, and TSP2 were significantly higher exp

253 chemistry, and flow cytometry, we found that PDGFRA-mutant GISTs harbored more immune cells with incr

254 ling of clinical tumor samples revealed that PDGFRA was the most highly expressed kinase gene among s

255 al sarcoma disease subtypes, suggesting that PDGFRA may be uniquely significant for synovial sarcomas

256 The PDGFRA(Delta8, 9) mutant was common, being present in 40

257 The PDGFRA(pos):Lin(neg):THY1(neg):DDR2(neg) cells were bipo

258 sert domain receptor (KDR) (VEGFRII) and the PDGFRA gene, and six cases of PDGFRA(Delta8, 9), an intr

259 A subset of cardiac FAPs, identified by the PDGFRA(pos):Lin(neg):THY1(neg):DDR2(neg) signature, expr

260 nalysis in TAPVR patients that implicate the PDGFRA gene in the development of TAPVR.

261 tions were also identified, including in the PDGFRA and JAK3 genes.

262 5.5]) and 37 (66%) of the 56 patients in the PDGFRA D842V population (median follow-up of 15.9 months

263 In the PDGFRA D842V-mutant population, 49 (88%; 95% CI 76-95) o

264 cover a recurrent cell-level mutation in the PDGFRA gene that is highly correlated with a well-known

265 We investigated the PDGFRA locus in PDGFRA-amplified gliomas and identified

266 I1 reexpression also resulted in loss of the PDGFRA and EGFR proteins, suggesting a rapid turnover of

267 T to imatinib depends on the location of the PDGFRA mutation; for example, the V561D juxtamembrane do

268 nd confers higher oncogenic potency than the PDGFRA mutation.

269 no or limited efficacy in patients with the PDGFRA D842V mutation or patients with GIST lacking KIT

270 e results suggest the possibility that these PDGFRA mutants behave as oncogenes in this subset of gli

271 All three PDGFRA isoforms are fully constitutively activated, inse

272 Thus, PDGFRA/NG2 cells act predominantly as a reservoir of new

273 HLA binding, both of which may contribute to PDGFRA-mutant GIST immunogenicity.

274 escribed in gastrointestinal stromal tumors (PDGFRA mutations) as well as in chronic myeloid leukemia

275 a model in which overexpression of wild-type PDGFRA associated with NF1 deficiency leads to aberrant

276 Addition of wild-type PDGFRA decreases latency and increases tumor invasion, w

277 terestingly, overexpression of the wild-type PDGFRA was even more potent in promoting transformation

278 terestingly, overexpression of the wild-type PDGFRA was even more potent in promoting transformation

279 of human MPNSTs have expression of wild-type PDGFRA, whereas only 5% harbor activating mutations of t

280 of human MPNSTs have expression of wild-type PDGFRA, whereas only 5% harbor activating mutations of t

281 os overexpressing mutant, but not wild-type, PDGFRA, suggesting a mechanism through which the oncogen

282 study included patients with an unresectable PDGFRA D842V-mutant gastrointestinal stromal tumour rega

283 f in IDH wild-type gliomaspheres upregulates PDGFRA and increases proliferation.

284 of nilotinib as a treatment option for V561D-PDGFRA-associated GIST, although the reduced sensitivity

285 d potent activity in vitro against the V561D-PDGFRA mutant but were significantly less efficacious ag

286 PKC412 potently inhibited the V561D-PDGFRA mutant in vitro and the D842V-PDGFRA mutant in vi

287 To determine whether PDGFRA is also targeted by more subtle mutations missed

288 d that PDGFRB informed poor prognosis, while PDGFRA was a positive prognostic factor.

289 with hypereosinophilic MPNs associated with PDGFRA and PDGFRB fusion genes are responsive to imatini

290 to activation of Rac1 in human cancers with PDGFRA amplification.

291 of the glioblastoma multiformes (GBMs) with PDGFRA amplification.

292 ggest that more than one third of GISTs with PDGFRA mutations may respond to imatinib and that mutati

293 sphorylated KIT oncoproteins interacted with PDGFRA, PDGFRB, phosphatidylinositol 3-kinase (PI3-K) an

294 er with the investigators that patients with PDGFRA D842V mutations would be analysed separately; the

295 In the safety population (patients with PDGFRA D842V-mutant gastrointestinal stromal tumour from

296 e dose-escalation part and all patients with PDGFRA D842V-mutant gastrointestinal stromal tumour in t

297 d activity was assessed in all patients with PDGFRA D842V-mutant gastrointestinal stromal tumour who

298 In this small phase 2 trial, patients with PDGFRA-negative hypereosinophilic syndrome who received

299 menon is especially common among tumors with PDGFRA amplification: overall, 43% of PDGFRA-amplified G

300 or other hypereosinophilic syndromes without PDGFRA or PDGFRB rearrangements.