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 mutations can explain response and sensitivity to

5 PDGFRA was the predominant target of focal amplification

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

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

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

9 4 astrocytomas and included the MDM4 (1q32), PDGFRA (4q12), MET (7q21), CMYC (8q24), PVT1 (8q24), WNT

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

11 All seven GIST cases with a PDGFRA mutation were DOG1-positive, while most of these

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

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

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

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

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

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

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

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

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

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

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

23 of the Fip1-like 1 (FIP1L1) and PDGFR alpha (PDGFRA) genes has been identified as a therapeutic targe

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

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

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

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

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

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

30 atelet-derived growth factor receptor alpha (PDGFRA) fusion was also documented in enriched eosinophi

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

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

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

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

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

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

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

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

39 atelet-derived growth factor receptor alpha (PDGFRA) that are potential therapeutic targets for imati

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

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

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

43 KIT-related kinase gene PDGF receptor alpha (PDGFRA), which occurred in either exon 18 (5.6%) or 12 (

44 atelet-derived growth factor receptor alpha (PDGFRA).

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

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

47 atelet-derived growth factor receptor-alpha (PDGFRA), has been invariably associated with a primary e

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

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

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

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

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

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

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

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

56 s of signature receptors, including EGFR and PDGFRA.

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

58 n, the role of mutation screening in KIT and PDGFRA as a diagnostic and prognostic aid is emphasized

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

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

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

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

63 We determined the KIT and PDGFRA mutation status of 1,105 unique GISTs using a com

64 cluding 127 GIST cases for which the KIT and PDGFRA mutation status was known.

65 ion profiling of 26 GISTs with known KIT and PDGFRA mutational status.

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

67 Thus, KIT and PDGFRA mutations appear to be alternative and mutually e

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

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

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

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

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

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

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

75 disorder, and at least two genes (c-kit and PDGFRA) with pathogenetically relevant mutations have be

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

77 GISTs (12%) were wild type for both KIT and PDGFRA.

78 other HSP90 client proteins, beyond KIT and PDGFRA.

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

80 situ hybridization probes for DOG1, KIT, and PDGFRA.

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

82 ed proteins (CTGF, CYR61, CX3CL1, TGFB1, and PDGFRA), and extracellular matrix protein (COL1A1).

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

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

85 elet-derived growth factor receptor A and B (PDGFRA and PDGFRB) tyrosine kinases.

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

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

88 hose that lack KIT expression and/or contain PDGFRA mutations.

89 acted in a cooperative fashion against D842V-PDGFRA.

90 significantly less efficacious against D842V-PDGFRA.

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

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

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

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

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

96 estores insulator function and downregulates PDGFRA.

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

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

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

100 FIP1L1-PDGFRA is a relatively infrequent but treatment-relevant

101 FIP1L1-PDGFRA+ mast cell disease responds completely to imatini

102 l deletion involving chromosome 4q12 (FIP1L1-PDGFRA).

103 mplete and durable responses in all 8 FIP1L1-PDGFRA(+) cases treated.

104 SH)-based strategy was used to detect FIP1L1-PDGFRA in bone marrow cells.

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

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

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

108 row mast cell infiltration pattern in FIP1L1-PDGFRA(+) SMCD-eos was distinctly diffuse with loose tum

109 se is now possible; Asp816Val c-kit+, FIP1L1-PDGFRA+, and molecularly undefined cases.

110 A novel oncogenic mutation (FIP1L1-PDGFRA), which results in a constitutively activated pla

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

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

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

114 To investigate the role of FIP1L1-PDGFRA in the pathogenesis of acute leukemia, we screene

115 abnormality, whereas the incidence of FIP1L1-PDGFRA in the remaining 81 patients with primary eosinop

116 a rational basis for the treatment of FIP1L1-PDGFRA positive chronic eosinophilic leukemia and mastoc

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

118 as an in vitro model for the study of FIP1L1-PDGFRA-positive chronic eosinophilic leukemia and for th

119 ukemia cell lines for the presence of FIP1L1-PDGFRA.

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

121 S and CEL and the implications of the FIP1L1-PDGFRA discovery on their diagnosis, classification, and

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

123 The discovery of the FIP1L1-PDGFRA fusion gene in the hypereosinophilic syndrome is

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

125 The FIP1L1-PDGFRA fusion gene is generated by a cryptic interstitia

126 In addition, the FIP1L1-PDGFRA fusion gene was also identified in cases with sys

127 The FIP1L1-PDGFRA fusion gene was subsequently detected in 9 of 16

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

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

130 y 40% of responding patients lack the FIP1L1-PDGFRA fusion, suggesting genetic heterogeneity.

131 One cell line, EOL-1, expressed the FIP1L1-PDGFRA fusion.

132 locus at 4q12 as a surrogate for the FIP1L1-PDGFRA fusion.

133 While all 3 patients with the FIP1L1-PDGFRA rearrangement achieved a sustained complete respo

134 Screening for the FIP1L1-PDGFRA rearrangement and Asp816Val mutation will advance

135 These observations suggest that the FIP1L1-PDGFRA rearrangement occurs in an early hematopoietic pr

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

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

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

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

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

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

142 in-5 (IL-5) levels or presence of the FIP1L1/PDGFRA mutation.

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

144 receptors despite increased mRNA levels for PDGFRA.

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

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

147 t-derived growth factor receptor-alpha gene (PDGFRA) to an uncharacterized human gene FIP1-like-1 (FI

148 t-derived growth factor receptor alpha gene (PDGFRA).

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

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

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

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

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

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

155 However, KIT expression can be low in PDGFRA-mutant GISTs, increasing the likelihood of misdia

156 d with the appearance of a T674I mutation in PDGFRA that confers resistance to imatinib.

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

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

159 may aid in the diagnosis of GISTs, including PDGFRA mutants that fail to express KIT antigen, and lea

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

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

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

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

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

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

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

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

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

169 KIT/PDGFRA mutational status was determined for 78 patients

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

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

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

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

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

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

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

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

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

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

180 consolidate GIST therapeutic response to KIT/PDGFRA inhibition.

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

182 (58%), KIT exon 11 (34%), and wild-type KIT/PDGFRA (56%).

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

184 st GISTs and hence may serve, along with KIT/PDGFRA, as a novel therapeutic target.

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

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

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

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

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

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

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

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

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

194 Comparative studies of KIT-mutant, PDGFRA-mutant, and wild-type GISTs indicate that there a

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

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

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

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

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

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

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

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

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

204 antibody against the extracellular domain of PDGFRA.

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

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

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

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

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

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

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

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

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

214 ll KIT mutant isoforms, but only a subset of PDGFRA mutant isoforms, were sensitive to imatinib, in v

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

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

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

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

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

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

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

222 Activating mutations of KIT or PDGFRA are found in the vast majority of GISTs, and the

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

224 mutation or no detectable mutation of KIT or PDGFRA had PR rates of 47.8% (P =.0006) and 0.0% (P <.00

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

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

227 pending on the exonic location of the KIT or PDGFRA mutation.

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

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

230 eutic targets in GISTs containing the KIT or PDGFRA mutational types with which they are associated.

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

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

233 Tumors expressing KIT or PDGFRA oncoproteins were indistinguishable with respect

234 Oncogenic KIT or PDGFRA receptor tyrosine kinase mutations are compelling

235 s require oncogenic activation of the KIT or PDGFRA receptor tyrosine kinase proteins, and the genomi

236 GISTs express oncogenic forms of the KIT or PDGFRA receptor tyrosine kinase proteins, which serve as

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

238 which are known to have key roles in KIT or PDGFRA signaling, and which might therefore contribute t

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

240 Activating mutations of KIT or PDGFRA were found in 112 (88.2%) and six (4.7%) GISTs, r

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

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

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

244 mediated by constitutively activated KIT or PDGFRA.

245 atinib were examined for mutations of KIT or PDGFRA.

246 Fip1-like 1 (FIP1L1) gene to the PDGFRalpha (PDGFRA) gene generated by an interstitial deletion on ch

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

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

249 ] showed expression of highly phosphorylated PDGFRA.

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

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

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

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

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

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

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

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

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

259 BA/F3 cell lines stably expressing selected PDGFRA mutant isoforms supported these findings.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

274 vating mutations of either the PDGFRB or the PDGFRA gene.

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

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

277 All three PDGFRA isoforms are fully constitutively activated, inse

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

279 esults indicate that the fusion of FIP1L1 to PDGFRA occurs rarely in leukemia cell lines, but they id

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.