ライフサイエンスコーパス: IDH

1 IDH mutant gliomas thus manifest a CpG island methylator

2 IDH mutation has been found to be an inciting event in g

3 IDH mutation is a central and defining event in the deve

4 IDH mutation is an early event in gliomagenesis and has

5 IDH mutational status identified patients with oligodend

6 IDH mutational status was also of prognostic significanc

7 IDH mutations are a favorable prognostic factor for huma

8 IDH mutations cause loss of native enzymatic activities

9 IDH status was evaluable in 210 of 291 patients; 156 (74

10 IDH-mt tumors have a more favorable prognosis, and tumor

11 IDH-mutant patients with 2HG levels >200 at complete rem

12 IDH-wt tumors are not a homogeneous entity and warrant f

13 SRSF2 mutations and advanced age (P < .01), IDH mutations (P < .01), and higher DIPSS-plus risk cate

14 an T-cell lymphotropic virus type 1 (HTLV-1; IDH) is a chronic recurrent eczema affecting HTLV-1-infe

15 stemic cancers, 31 other CNS-tumors, and 120 IDH-mutant cartilaginous tumors, we identified that the

16 on subsequent mutational analysis of the 13 IDH wild-type samples with 2HG levels >700 ng/mL, 9 were

17 P, and 1 CBL, 1 CBLB, 4 TET2, 2 ASXL1, and 2 IDH family mutations in myeloid BP.

18 xyglutarate (2-HG), a product of the altered IDH protein.

19 s have chromosomes 1p/19q co-deletion and an IDH mutation.

20 Results Nine patients had an IDH-1 mutation and 61 had IDH-1 wild type.

21 enesis and tumor maintenance and identify an IDH-independent strategy to target these cancers therape

22 make a presumptive molecular diagnosis of an IDH mutation in gliomas technically unable to undergo a

23 pects of this phenotype in the absence of an IDH mutation.

24 Patients who had lower-grade gliomas with an IDH mutation and 1p/19q codeletion had the most favorabl

25 Lower-grade gliomas with an IDH mutation either had 1p/19q codeletion or carried a T

26 e majority of lower-grade gliomas without an IDH mutation had genomic aberrations and clinical behavi

27 Most lower-grade gliomas without an IDH mutation were molecularly and clinically similar to

28 er than those observed in samples without an IDH mutation, similar to what was observed in the origin

29 lus (P = .01; HR = 1.9; 95% CI, 1.1-3.0) and IDH mutations (P < .01; HR = 2.3; 95% CI, 1.4-3.8).

30 cluded indirect hyperbilirubinemia (12%) and IDH-inhibitor-associated differentiation syndrome (7%).

31 s indicate that CBL family, TET2, ASXL1, and IDH family mutations and additional cryptic karyotypic a

32 patients, virtually all 1p19q codeleted and IDH mutated (59 of 60).

33 ations in the metabolic enzymes SDH, FH, and IDH can result in cancer and, more broadly, for how alte

34 aracterization may be useful for grading and IDH mutation detection of gliomas and requires only 7 mi

35 y, combination of CNTFRalpha methylation and IDH mutation significantly (p < 0.05) improved the progn

36 isocitrate dehydrogenase (IDH-1)-mutated and IDH-1 wild-type glioblastomas.

37 i.e., were triple-positive), 5% had TERT and IDH mutations, 45% had only IDH mutations, 7% were tripl

38 han 1% were triple-positive, 2% had TERT and IDH mutations, 7% had only IDH mutations, 17% were tripl

39 As expected, TET2 and IDH mutated patients had significantly lower levels of 5

40 is divided into IDH wild-type ( IDH-wt) and IDH-mt tumors.

41 -Olff-Fresco multi-model selection approach, IDH testing was done.

42 ed to study new tumor tissue markers such as IDH mutations.

43 Cancer-associated IDH mutations alter the enzymes such that they reduce 2O

44 LGG-associated IDH mutations confer gain-of-function activity by conver

45 r subset also harbors LNK, CBL, TET2, ASXL1, IDH, IKZF1, or EZH2 mutations; the precise pathogenetic

46 acy of vaccine immunotherapy in mice bearing IDH-MUT gliomas.

47 We establish a firm association between IDH mutations and serum 2HG concentration in AML, and co

48 vivo (1)H-MRS spectra discriminated between IDH-mutant tumors and healthy tissue, and separated IDH1

49 se studies provide a functional link between IDH mutations, hepatic cell fate, and IHCC pathogenesis,

50 Differences in bulk profiles between IDH-mutant astrocytoma and oligodendroglioma can be prim

51 nt changes in the maximum activities of both IDH and G6PD, but not in triglyceride concentration, sug

52 godendroglioma requires the presence of both IDH-mt and 1p/19q co-deletion, whereas anaplastic astroc

53 glioma that were captured more accurately by IDH, 1p/19q, and TP53 status than by histologic class.

54 ctive modulation of relevant cancer genes by IDH mutations.

55 nt of D2HGA and suggest that 2HG produced by IDH mutant tumors has the potential to provoke a paraneo

56 L10 and T cell accumulation were reversed by IDH-C35, a specific inhibitor of mutant IDH1.

57 tion with kinetic data on IDHKP to calculate IDH activity at a range of total IDH levels and find tha

58 bond with a concomitant decrease in cellular IDH activity was observed during the stationary phase fo

59 Patients with classic IDH lesions who are serologically negative should be inv

60 E. coli IDH is regulated by reversible phosphorylation catalyzed

61 Conclusion IDH-mutated glioblastomas have a less invasive phenotype

62 tly lower in human glioma tissues containing IDH mutations than in gliomas without such mutations.

63 The alpha-D181N IDH mutant exhibits a 2000-fold decrease in Vmax, with i

64 e gene coding for isocitrate dehydrogenase ( IDH).

65 Mutant isocitrate dehydrogenase (IDH) 1 and 2 proteins alter the epigenetic landscape in

66 ibitors of mutated isocitrate dehydrogenase (IDH) 1 and IDH2, antibody-based therapies, and cell-base

67 rogression such as isocitrate dehydrogenase (IDH) 1, IDH2, EZH2, serine/arginine-rich splicing factor

68 Mutations in isocitrate dehydrogenase (IDH) are the most prevalent genetic abnormalities in low

69 c mutations in the isocitrate dehydrogenase (IDH) enzymes through a genome-wide mutational analysis i

70 ions involving the isocitrate dehydrogenase (IDH) enzymes.

71 haracterization of isocitrate dehydrogenase (IDH) gene mutation status of gliomas.

72 onal status of the isocitrate dehydrogenase (IDH) gene were determined.

73 Isocitrate dehydrogenase (IDH) genes 1 and 2 are frequently mutated in acute myelo

74 c mutations in the isocitrate dehydrogenase (IDH) genes IDH1 and IDH2 occur frequently in acute myelo

75 the genes encoding isocitrate dehydrogenase (IDH) has uncovered a critical role for altered metabolis

76 e metabolic enzyme isocitrate dehydrogenase (IDH) in subsets of cancers, including secondary glioblas

77 uman NAD-dependent isocitrate dehydrogenase (IDH) is a heterotetrameric mitochondrial enzyme with 2al

78 Isocitrate dehydrogenase (IDH) is a reversible enzyme that catalyzes the NADP(+)-d

79 uman NAD-dependent isocitrate dehydrogenase (IDH) is allosterically activated by ADP by lowering the

80 ies, NAD+-specific isocitrate dehydrogenase (IDH) is believed to control flux through the tricarboxyl

81 er of novel genes, isocitrate dehydrogenase (IDH) is recurrently mutated in intrahepatic cholangiocar

82 Mutations of the isocitrate dehydrogenase (IDH) metabolic enzymes IDH1 and IDH2 have been found to

83 hways disturbed in isocitrate dehydrogenase (IDH) mutant tumors revealed that the hallmark metabolic

84 tions, such as the isocitrate dehydrogenase (IDH) mutations found in 15% of AML patients.

85 Cancer-associated isocitrate dehydrogenase (IDH) mutations produce the metabolite 2-hydroxyglutarate

86 lastomas harboring isocitrate dehydrogenase (IDH) mutations, but metabolic alterations in glioblastom

87 ling, but not with isocitrate dehydrogenase (IDH) mutations, suggesting a distinct mechanism for incr

88 ycle NAD+-specific isocitrate dehydrogenase (IDH) of Saccharomyces cerevisiae is an octameric enzyme

89 scale variation in isocitrate dehydrogenase (IDH) or glucose-6-phosphate dehydrogenase (G6PD) activit

90 vior arises in the isocitrate dehydrogenase (IDH) regulatory system of Escherichia coli, which was sh

91 hydratase (FH) and isocitrate dehydrogenase (IDH), advancing and challenging our understanding of cel

92 uman NAD-dependent isocitrate dehydrogenase (IDH), with three types of subunits present in the ratio

93 hese influences in isocitrate dehydrogenase (IDH)-mutant gliomas by combining 14,226 single-cell RNA

94 nsferase (OGT) and isocitrate dehydrogenase (IDH).

95 hosphate-dependent isocitrate dehydrogenase (IDH)1 and IDH2 frequently arise in human leukemias and o

96 Oncogenic isocitrate dehydrogenase (IDH)1 and IDH2 mutations at three hotspot arginine resid

97 phenotypes of both isocitrate dehydrogenase (IDH-1)-mutated and IDH-1 wild-type glioblastomas.

98 verse flux through isocitrate dehydrogenase, IDH).

99 Isocitrate dehydrogenases (IDH) convert isocitrate to alpha-ketoglutarate (alpha-KG

100 factors: mutated isocitrate dehydrogenases (IDH), succinate dehydrogenase (SDH), and fumarate hydrat

101 for artificial valve replacement, developed IDH and esophagogastroduodenal pneumatosis after endosco

102 To examine the effect of endogenous IDH mutations and 2-HG, we created a panel of isogenic e

103 The results strongly suggest that eukaryotic IDH enzymes are exquisitely tuned to ensure that alloste

104 ninvasive biomarkers of disease activity for IDH-mutant AML.

105 a noninvasive clinical imaging biomarker for IDH-mutated gliomas.

106 ds-ratios were 9.25 (5.17-16.52; 95% CI) for IDH-mutated gliomas and 12.85 (5.94-27.83; 95% CI) for I

107 d gliomas and 12.85 (5.94-27.83; 95% CI) for IDH-mutated, 1p/19q co-deleted gliomas.

108 r samples underwent immunohistochemistry for IDH-1 R132H mutations.

109 Our work provides a unifying model for IDH-mutant gliomas and a general framework for dissectin

110 howed the highest diagnostic performance for IDH gene mutation detection in low-grade glioma (AUC, 0.

111 t differences can regulate the potential for IDH mutations to produce 2HG in cells.

112 ation that can improve patient selection for IDH-targeted therapies.

113 omas (LGGs) are fundamentally different from IDH-mutant LGGs occurring in adults, because they rarely

114 ed replication plan of key experiments from "IDH mutation impairs histone demethylation and results i

115 Gain-of-function IDH mutations are initiating events that define major cl

116 Furthermore, IDH-C35 enhanced the efficacy of vaccine immunotherapy i

117 ne patients had an IDH-1 mutation and 61 had IDH-1 wild type.

118 levels >700 ng/mL, 9 were identified to have IDH mutations.

119 Intramural duodenal hematoma (IDH) rarely occurs after endoscopic intervention.

120 These data broaden our understanding of how IDH mutations may contribute to cancer through either ne

121 Here we show that human IDH mutant gliomas exhibit hypermethylation at cohesin a

122 The Intermediate Disturbance Hypothesis (IDH) is well-known in ecology providing an explanation f

123 value of metabolite screening in identifying IDH-mutated tumors associated with elevated oncometaboli

124 r mechanism that defines chemosensitivity in IDH-mutated gliomas.

125 a-inducible chemokines, including CXCL10, in IDH-mutated (IDH-MUT) tumors compared with IDH-WT tumors

126 he latter strain suggests that a decrease in IDH activity is important for metabolic changes in stati

127 from 10 to 30 000 ng/mL and were elevated in IDH-mutants (median, 3004 ng/mL), compared to wild-type

128 demonstrate a mechanism of immune evasion in IDH-MUT gliomas and suggest that specific inhibitors of

129 last 2-HG levels are significantly higher in IDH-mutant patients, with a correlation between baseline

130 SPR-mediated disruption of the CTCF motif in IDH wild-type gliomaspheres upregulates PDGFRA and incre

131 ognostic markers and outcome of mutations in IDH genes encoding isocitrate dehydrogenases in adult de

132 Hotspot mutations in IDH isoforms 1 or 2 occur in approximately 15% of intrah

133 mutations in the TERT promoter, mutations in IDH, and codeletion of chromosome arms 1p and 19q (1p/19

134 Mutations in IDH, TP53, and ATRX and codeletion of chromosome arms 1p

135 ests that IDH may be a therapeutic target in IDH-mutant gliomas.

136 background and of smaller-scale variation in IDH, G6PD, and malic enzyme across 10 different genetic

137 formation of a disulfide bond that inhibits IDH activity.

138 ereas anaplastic astrocytoma is divided into IDH wild-type ( IDH-wt) and IDH-mt tumors.

139 ted by a strain (idh1Deltaidh2Delta) lacking IDH.

140 for the IDH1(R132H) mutation exhibited less IDH-mediated production of NADPH, such that after exposu

141 We leveraged IDH wild-type glioblastomas, derivative neurospheres, an

142 lar to previous reports on related mammalian IDH enzymes.

143 sting compensatory interactions between MEN, IDH, and G6PD.

144 evels by positively modulating mitochondrial IDH activity and inducing IDH2 expression.

145 anner independent of wild-type mitochondrial IDH function.

146 monoallelic IDH1 mutation when mitochondrial IDH flux was diverted to the cytosol.

147 Moreover, IDH and Kras mutations, genetic alterations that co-exis

148 Mutant IDH produces 2-hydroxyglutarate (2HG), which induces his

149 Mutant IDH protein produces a new onco-metabolite, 2-hydroxyglu

150 Mutant IDH proteins in IHCC and other malignancies acquire an a

151 gression-free survival after CRT, and mutant IDH was associated with longer overall survival (9.4 v 5

152 cular mechanisms of transformation by mutant IDH and discuss their implications for the development o

153 For AML, low-grade glioma and CC, mutant IDH status is associated with a DNA hypermethylation phe

154 Introduction of either mutant IDH or cell-permeable 2HG was associated with repression

155 In the cells types examined, mutant IDH-induced EMT is dependent on up-regulation of the tra

156 ly engineered mouse models expressing mutant IDH in the adult liver show an aberrant response to hepa

157 How mutant IDH and 2-HG alter signaling pathways to promote cancer,

158 biting production of the substrate of mutant IDH enzymes caused slow-down of glioma cell growth.

159 ial implications for understanding of mutant IDH function and for optimizing therapeutic approaches t

160 strating that continued expression of mutant IDH is required to maintain this phenotype.

161 d suggest that specific inhibitors of mutant IDH may improve the efficacy of immunotherapy in patient

162 ansformation, but the contribution of mutant IDH proteins to maintenance and progression of AML in vi

163 propagating downstream the effects of mutant IDH, leading to malignant transformation of cells.

164 roxyglutarate, supporting the role of mutant IDH-produced 2-hydroxyglutarate as an inhibitor of TET-m

165 table transfection of a 2HG-producing mutant IDH into immortalized astrocytes resulted in progressive

166 These results suggest mutant IDH proteins can reversibly deregulate discrete signalin

167 he therapeutic potential of targeting mutant IDH enzymes will be discussed.

168 Here we show that mutant IDH blocks liver progenitor cells from undergoing hepato

169 Cells expressing the mutant IDH are thus deficient in their capacity for reductive c

170 P = .037) in low-grade glioma with a mutated IDH gene, and MTI was significantly increased in glioma

171 hemokines, including CXCL10, in IDH-mutated (IDH-MUT) tumors compared with IDH-WT tumors.

172 o the presence or absence of IDH mutations ( IDH-mt) and combined 1p/19q loss.

173 cept for isocitrate dehydrogenase mutations (IDH(mut)) that were almost mutually exclusive with TET2(

174 f NAD-specific isocitrate dehydrogenase (NAD-IDH, or IDH3), which is believed to catalyze the oxidati

175 retina has a particular requirement for NAD-IDH.

176 ggest that the active sites of the human NAD-IDH are shared between alpha and gamma subunits and betw

177 rosines of each of the subunits of human NAD-IDH, the tyrosines were mutated (one subunit at a time)

178 dividuals had a substantial reduction of NAD-IDH activity, with about a 300-fold increase in the K(m)

179 ines in the three dissimilar subunits of NAD-IDH thus have distinctive functions.

180 that mitochondrial NADP-IDH, rather than NAD-IDH, serves as the main catalyst for this reaction in th

181 NADP-specific isocitrate dehydrogenase (NADP-IDH, or IDH2), an enzyme that catalyzes the same reactio

182 Escherichia coli and pig mitochondrial NADP-IDH and sequence alignments.

183 pport the hypothesis that mitochondrial NADP-IDH, rather than NAD-IDH, serves as the main catalyst fo

184 ed cells, we tested the effect of neomorphic IDH mutants on adipocyte differentiation in vitro.

185 rs lived longest, patients with noncodeleted IDH-mutated tumors also lived longer after CRT.

186 To test whether the ability of IDH mutants to promote histone methylation contributes t

187 Differences were noted in the ability of IDH mutations to cause robust 2-HG accumulation.

188 rily according to the presence or absence of IDH mutations ( IDH-mt) and combined 1p/19q loss.

189 siological role for allosteric activation of IDH during changes in environmental conditions.

190 ogical and dermatological characteristics of IDH are described, and their principal diagnostic criter

191 tic performance for grading and detection of IDH gene mutation status.

192 ed an obligatory factor for the diagnosis of IDH.

193 A tetrameric form of IDH (an IDH1(G15D)/IDH2 mutant enzyme) demonstrated half

194 rther demonstrated using a monomeric form of IDH from Azotobacter vinelandii, which can be shown to g

195 oped to specifically inhibit mutant forms of IDH (mIDH1 and mIDH2).

196 trains expressing regulatory mutant forms of IDH are likely to correlate with the slight reductions i

197 e or catalytically deficient mutant forms of IDH exhibited rapid respiratory transitions, whereas str

198 Finally, by expressing mutant forms of IDH in vivo, we determined that detrimental effects on l

199 ains expressing well defined mutant forms of IDH or a non-allosteric bacterial NAD+-specific isocitra

200 trains expressing regulatory mutant forms of IDH or the bacterial IDHa enzyme exhibited much slower r

201 usly reported, expression of mutant forms of IDH with severe catalytic defects but intact regulatory

202 We constructed two mutant forms of IDH, one containing a C150S substitution in IDH2 and the

203 te relationship between the phospho-forms of IDH.

204 s, and the neomorphic, oncogenic function of IDH mutations affects several epigenetic and gene regula

205 A demethylation and poor outcome; a group of IDH-wild-type diffuse glioma showed molecular similarity

206 of the system (including homodimerization of IDH and bifunctionality of IDHKP) that provide a potenti

207 athway and offer insights into the impact of IDH mutation and D-2HG on metazoan tissues.

208 findings, we have investigated the impact of IDH mutations on the immunological milieu in LGG.

209 dditionally, we observed that independent of IDH mutation status, methylation of CNTFRalpha was signi

210 kinase/phosphatase (IDHKP), and the level of IDH activity determines whether carbon flux is directed

211 porating 2HG MRS into clinical management of IDH-mutated gliomas.

212 The mechanisms of IDH mutations in gliomagenesis, and their value as diagn

213 novel genetically engineered mouse model of IDH-driven malignancy.

214 endroglioma is characterized by mutations of IDH and CIC, 1p/19q loss, and slow growth.

215 The recurring nature of IDH was a characteristic found in all cases.

216 The onset of IDH may occur earlier than reported in the literature.

217 reviously been linked to the pathogenesis of IDH mutant tumors.

218 that is highly dependent on the presence of IDH mutation.

219 defective in both of the normal reactions of IDH.

220 Here we discuss the relevance of IDH mutations to leukemia pathogenesis, therapy, and out

221 s a number of other single-sample reports of IDH non-synonymous mutation, did not elevate cellular 2H

222 Elucidation of the role of IDH mutations and (R)-2HG in leukemogenesis has been ham

223 To further understand the role of IDH mutations in cancer, we conducted mechanistic studie

224 In order to investigate the role of IDH mutations in immune response, we created a syngeneic

225 mechanism for a non-2HG-producing subset of IDH mutations in some malignancies.

226 A subtype of IDH mutant glioma was associated with DNA demethylation

227 Treatment of IDH mutant gliomaspheres with a demethylating agent part

228 dings may have implications for treatment of IDH-mutant leukemia.

229 t advances in glioma classification based on IDH mutation and 1p/19q co-deletion status were recapitu

230 , 2% had TERT and IDH mutations, 7% had only IDH mutations, 17% were triple-negative, and 74% had onl

231 5% had TERT and IDH mutations, 45% had only IDH mutations, 7% were triple-negative, and 10% had only

232 rs) among patients who had gliomas with only IDH mutations and was highest (59 years) among patients

233 n of patients who exhibited TET2(mut) and/or IDH(mut) revealed shorter overall survival (P = .03), al

234 without 1p/19q co-deletion [IDHmt/codel], or IDH wild type [IDHwt]; p=0.013).

235 a-free survival, karyotype, or JAK2, MPL, or IDH mutations.

236 ted almost entirely of patients with TET2 or IDH mutations.

237 cells with defective mitochondria, oxidative IDH flux persists and may exceed the reductive flux.

238 In tumour samples from glioma patients, IDH mutations were associated with a distinct gene expre

239 Here we report that 2HG-producing IDH mutants can prevent the histone demethylation that i

240 -2-hydroxyglutarate was sufficient to reduce IDH-mediated NADPH production and increase IR sensitivit

241 n, although we cannot rule out net reductive IDH flux in some compartments.

242 by spreading of label without net reductive IDH flux.

243 Results IDH mutations were found in 33% of the patients.

244 nd G-CIMP+ primary gliomas and can segregate IDH wild-type and mutated tumors as well as those exhibi

245 pes, helping to identify tumors with similar IDH mutations.

246 llosteric, hetero-octameric, NAD(+)-specific IDH from yeast in three forms: 1) without ligands, 2) wi

247 treating AML and other cancers by targeting IDH mutant proteins, it remains unclear how these mutant

248 and monitoring treatment response targeting IDH mutations.

249 timizing therapeutic approaches to targeting IDH-mutant tumors.

250 Our findings demonstrate that IDH mutation is the molecular basis of CIMP in gliomas,

251 ng of chondrosarcoma biopsies and found that IDH mutations were associated with DNA hypermethylation

252 Early evidence suggests that IDH may be a therapeutic target in IDH-mutant gliomas.

253 Our study suggests that IDH mutations promote gliomagenesis by disrupting chromo

254 Among the IDH-1 wild-type tumors, 42 of 61 (69%) were diffusively

255 melanoma development and directly links the IDH and TET activity-dependent epigenetic pathway to 5-h

256 nt studies have shown that expression of the IDH mutant enzymes results in high levels of 2HG and a b

257 ma cultures recapitulates the effects of the IDH mutation on intrinsic apoptosis, shuts down oxidativ

258 nifies much of the known biochemistry of the IDH regulatory system into a single quantitative framewo

259 Here we show that the IDH variants in CS are also associated with a hypermethy

260 ty and forest disturbance expected under the IDH; instead diversity peaked in old-growth forests.

261 Here, we used the IDH as a framework to describe the role of forest distur

262 H mutation (P = .013) when compared with the IDH wild-type counterparts.

263 Therefore, IDH flux may not be a net contributor to acetyl-CoA prod

264 The three IDH isoforms (nicotinamide adenine dinucleotide phosphat

265 silenced in oligodendrogliomas secondary to IDH-associated hypermethylation and 1p allelic loss.

266 ntified that the association was specific to IDH-mutant gliomas.

267 o calculate IDH activity at a range of total IDH levels and find that our model predicts robustness.

268 e development of targeted therapies to treat IDH mutant malignancies.

269 (median, 3004 ng/mL), compared to wild-type IDH (median, 61 ng/mL) (P < .0005).

270 alterations in glioblastomas with wild-type IDH are poorly understood.

271 d a better outcome than those with wild-type IDH genes.

272 astrocytoma is divided into IDH wild-type ( IDH-wt) and IDH-mt tumors.

273 eterotetrameric interfaces in the unliganded IDH hetero-octamer are reduced in the ligand-bound forms

274 The following search terms were used: IDH, IDH1, IDH2, and isocitrate dehydrogenase, in conjun

275 iew of the literature dating from 2008, when IDH mutation was discovered to be clinically significant

276 The age at which IDH disappeared in the others was 10-20 years.

277 However, the molecular pathways by which IDH mutations lead to tumour formation remain unclear.

278 o the pathogenesis of tumors associated with IDH gene mutations.

279 gion at 8q24.21, is strongly associated with IDH-mutant glioma development and was suggested to be a

280 with high D-2HG levels in cancer cells with IDH mutations.

281 s are relatively common in PMF, cluster with IDH mutations, and are independently predictive of poor

282 have a less invasive phenotype compared with IDH wild type.

283 n IDH-mutated (IDH-MUT) tumors compared with IDH-WT tumors.

284 grade gliomas that were more concordant with IDH, 1p/19q, and TP53 status than with histologic class.

285 eloid leukemia (AML) patients correlate with IDH mutations, and whether diagnostic or remission 2HG m

286 h-risk karyotype; but did not correlate with IDH mutations.

287 ously published criteria and correlated with IDH-1 mutation status by using the Freeman-Halton extens

288 Mutations were mutually exclusive with IDH(mut), which supported recent data on a common mechan

289 Nearly all lower-grade gliomas with IDH mutations and no 1p/19q codeletion had mutations in

290 viable therapeutic strategy for gliomas with IDH mutations.Significance: These findings show that the

291 ificantly increased in glioma grade III with IDH mutation (P = .013) when compared with the IDH wild-

292 tral profiles were observed for lesions with IDH-mutated genotypes, between astrocytoma and oligodend

293 , there exist relatively few cell lines with IDH mutations.

294 All of the patients with IDH-1 mutation had a minimally invasive DT imaging pheno

295 e efficacy of immunotherapy in patients with IDH-MUT gliomas.

296 um and myeloblast samples from patients with IDH-mutant AML contain high levels of the metabolite 2-h

297 ar differentiation that can be reversed with IDH mutant-specific small-molecule inhibitors.

298 Those with IDH-1 wild-type were more likely to show no activity on

299 timally segregated patients with and without IDH mutations, and on subsequent mutational analysis of

300 associated with higher grade tumors without IDH mutations.