ライフサイエンスコーパス: CIMP

1 CIMP has been reported to be useful for predicting progn

2 CIMP high was defined as methylation at 2 or more of the

3 CIMP in CRC may result from activating mutations in eith

4 CIMP shifted the pressure-length relationship to the lef

5 CIMP+ tumors also have a high incidence of p16 and THBS1

6 CIMP-high HPs were present primarily in patients with a

7 CIMP-high unstable tumors also were more likely to have

8 uently contained BRAF mutations (P = .0041), CIMP-high (P = .013), and MSI-high (P = .037).

9 in 16 (70%) of 23 CIMP+ tumors, 1 (8%) of 12 CIMP intermediate tumors, and 1 (5%) of 21 CIMP- tumors

10 2 CIMP intermediate tumors, and 1 (5%) of 21 CIMP- tumors (P<0.0001).

11 lation of p16 was detected in 16 (70%) of 23 CIMP+ tumors, 1 (8%) of 12 CIMP intermediate tumors, and

12 Methylation status was evaluated using 6 CIMP-related markers (MINT1, MINT2, MINT31, p16(INK4alph

13 Methylation analysis of 7 CIMP-related markers revealed that the mean number of me

14 (52 of 108) of adenomas with 25% (19 of 76) CIMP-high (two or more methylated loci) and 32% (24 of 7

15 or more methylated loci) and 32% (24 of 76) CIMP-low (one methylated locus).

16 A CIMP-high (CIMP-H) subgroup, which exhibits an exception

17 A CIMP-low (CIMP-L) subgroup is enriched for KRAS mutation

18 entage of genes, whereas a subset displays a CIMP+ phenotype.

19 Although CIMP appears as a phenomenon that occurs in various canc

20 Although CIMP is probably the cause of high-frequency microsatell

21 at were hypermethylated in both non-CIMP and CIMP colon cancers when compared with normal colon.

22 ethylation profiles of normal, non-CIMP, and CIMP colon specimens.

23 clearly classified as normal, non-CIMP, and CIMP, thus signifying that these three groups have disti

24 These findings suggest that CIN and CIMP represent 2 independent and inversely related mecha

25 differentially clustered with CIMP-high and CIMP-low according to KRAS and BRAF status.

26 Pheterogeneity = 0.02, between CIMP-high and CIMP-low/CIMP-negative cancer risks).

27 was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis.

28 d and elevated levels of DNA methylation and CIMP+ tumors have distinctive clinicopathological and mo

29 th sham, CIMP was decreased in AVF mice, and CIMP protein transfer increased plasma and LV tissue lev

30 tula (AVF) was created in C57BL/J6 mice, and CIMP was administered to AVF and sham mice by protein tr

31 RAF mutation (V600E) and tested for MLH1 and CIMP methylation, the latter including the genes, CACNA1

32 nown that oxidative stress activates MMP and CIMP inhibits MMP, it is unclear whether CIMP administra

33 l factor required for INK4-ARF silencing and CIMP in CRCs containing activated KRAS.

34 votal factor required for MLH1 silencing and CIMP in CRCs containing BRAF(V600E).

35 sts the presence of KRAS mutation-associated CIMP subtype (CIMP-low, CIMP2).

36 ociations between methylation frequencies at CIMP-related markers and MSI or MSI-/LOH- sporadic CRCs

37 High levels of aberrant methylation at CIMP-related markers in MSH2-methylated tumors raise the

38 The mean methylation scores at CIMP-related markers were significantly higher in Lynch

39 ed as follows: sham; sham+CIMP; AVF; and AVF+CIMP (n=6).

40 rend = 0.25) (Pheterogeneity = 0.02, between CIMP-high and CIMP-low/CIMP-negative cancer risks).

41 There was a significant concordance between CIMP and the methylation of known genes including p16, a

42 These interactions between CIMP, K-RAS mutations, and p53 mutations were preserved

43 In SEM, the correlation structures between CIMP, locus-specific CpG island methylation, and MSI dif

44 C-CIMP was furthermore characterized by silencing of genes

45 lear cell CpG island methylator phenotype (C-CIMP) subgroup associated with promoter methylation of V

46 In sporadic colon cancer, CIMP has distinct epidemiologic and clinical features an

47 status in a panel of 14 markers (7 canonical CIMP-related loci and 7 new loci), microsatellite instab

48 correlate with mutant KRAS may help clarify CIMP in future studies.

49 ropose a robust new marker panel to classify CIMP+ tumors.

50 In contrast, the existence of a comparable CIMP subtype in gastric cancer (GC) has not been clearly

51 However, the current CIMP criteria are ambiguous and often result in an under

52 s, frequently observed in gliomas, establish CIMP in primary human astrocytes by remodeling the methy

53 The aim of this study was to evaluate CIMP in carcinoid tumors and PETs.

54 We therefore evaluated CIMP in 22 sporadic serrated adenomas and 6 serrated ade

55 for the elucidation of a molecular basis for CIMP.

56 1.31; p = 0.04), while it was beneficial for CIMP-High associated tumours (DFS; HR, 0.17; 95% CI, 0.0

57 Risk factors for CIMP-high-serrated lesions included Caucasian race, curr

58 uent mutations in BRAF, were more frequently CIMP- and MSI-high, and had a worse prognosis than solit

59 lation correlated with the less aggressive G-CIMP (Glioma CpG Methylator Phenotype) subset of GBM.

60 ent with those observed in IDH1-mutant and G-CIMP+ primary gliomas and can segregate IDH wild-type an

61 ylation analysis, we show that G-CIMP+ and G-CIMP-subtypes enrich distinct classes of biological proc

62 key gene expression programs, characterize G-CIMP-positive proneural glioblastomas but not other glio

63 Glioma CIMP (G-CIMP) is a powerful determinant of tumour pathogenicity,

64 iate-grade gliomas demonstrates a distinct G-CIMP phenotype that is highly dependent on the presence

65 itrate dehydrogenase 1 (IDH1), establishes G-CIMP by remodelling the methylome.

66 While the standard method for identifying G-CIMP tumors is based on genome-wide DNA methylation data

67 shion that mirrors the changes observed in G-CIMP-positive lower-grade gliomas.

68 lioma CpG island methylator phenotype (non-G-CIMP) primary tumors.

69 pathogenicity, but the molecular basis of G-CIMP remains unresolved.

70 IDH1 CNA had decreased 2HG, maintenance of G-CIMP, and DNA methylation reprogramming outside CGI.

71 glioma CpG island methylator phenotype, or G-CIMP tumors, have distinct genomic copy number aberratio

72 anifest a CpG island methylator phenotype (G-CIMP), although the functional importance of this altere

73 G island (CGI) hypermethylation phenotype (G-CIMP).

74 me-wide methylation analysis, we show that G-CIMP+ and G-CIMP-subtypes enrich distinct classes of bio

75 ted tumors as well as those exhibiting the G-CIMP phenotype in unsupervised analysis of two primary g

76 the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predic

77 oped and evaluated a method to predict the G-CIMP status of GBM samples based solely on gene expressi

78 ained all of the glioblastoma samples with G-CIMP, a known methylation phenotype driven by the IDH1 m

79 Glioma CIMP (G-CIMP) is a powerful determinant of tumour pathog

80 at period or without prior endoscopy to have CIMP and microsatellite instability.

81 A CIMP-high (CIMP-H) subgroup, which exhibits an exceptionally high f

82 However, CIMP-high unstable tumors were significantly more likely

83 11 of 21] vs. 14% [10 of 72], P = 0.004), in CIMP+ cases (40% [19 of 48] vs. 4% [2 of 46], P < 0.001)

84 ions: frequent K-RAS mutations were found in CIMP(+) CRCs (28/41, 68%) compared with CIMP(-) cases (1

85 26 sites were found to be hypermethylated in CIMP tumors only; and importantly, 80% of these sites we

86 es that acquired promoter DNA methylation in CIMP-H tumors.

87 that the additional hypermethylation seen in CIMP tumors occurs almost exclusively at CpG islands and

88 analyses defined a distinct superenhancer in CIMP+ colon cancers that regulates cMYC transcription.

89 hat were down-regulated more than twofold in CIMP-H tumors together with promoter DNA hypermethylatio

90 d previously for microsatellite instability, CIMP, and mutations of p53 and K-RAS.

91 A CIMP-low (CIMP-L) subgroup is enriched for KRAS mutations and char

92 MSI high or MSI low, CIMP high or CIMP low, CIMP negative, and positive or negative for BRAF and/or

93 satellite stable (MSS), MSI high or MSI low, CIMP high or CIMP low, CIMP negative, and positive or ne

94 f pathway-unassigned tumors (MSS or MSI low, CIMP negative, BRAF mutation negative, and KRAS mutation

95 e 2 (microsatellite stable [MSS] or MSI-low, CIMP-positive, positive for BRAF mutation, negative for

96 = 0.001), but not with the risk of CIMP-low/CIMP-negative cancer (Ptrend = 0.25) (Pheterogeneity = 0

97 neity = 0.02, between CIMP-high and CIMP-low/CIMP-negative cancer risks).

98 and cardiac inhibitor of metalloproteinase (CIMP) are coexpressed in the heart.

99 tation positive; n = 58), serrated (any MSI, CIMP high, BRAF mutation positive, and KRAS mutation neg

100 appear to be significantly modified by MSI, CIMP, LINE-1, or the other clinical and molecular variab

101 mutation negative; n = 170), alternate (MSS, CIMP low, BRAF mutation negative, and KRAS mutation posi

102 owing integrated pathways: traditional (MSS, CIMP negative, BRAF mutation negative, and KRAS mutation

103 Non-CIMP tumors are separated into two distinct clusters.

104 ntexts that were hypermethylated in both non-CIMP and CIMP colon cancers when compared with normal co

105 in BRAF and KRAS); and type 5 (MSI-high, non-CIMP, negative for mutations in BRAF and KRAS).

106 also transcriptionally down-regulated in non-CIMP subgroups, but this was not attributable to promote

107 sites that were also hypermethylated in non-CIMP tumors.

108 KRAS mutation); type 3 (MSS or MSI low, non-CIMP, negative for BRAF mutation, positive for KRAS muta

109 KRAS mutation); type 4 (MSS or MSI-low, non-CIMP, negative for mutations in BRAF and KRAS); and type

110 wide DNA methylation profiles of normal, non-CIMP, and CIMP colon specimens.

111 n could be clearly classified as normal, non-CIMP, and CIMP, thus signifying that these three groups

112 One non-CIMP subgroup is distinguished by a significantly higher

113 types, but it remains unclear whether or not CIMP is a universal phenomenon across human neoplasia or

114 , p53 mutations were found in 24% (10/41) of CIMP(+) CRCs vs. 60% (30/46) of CIMP(-) cases (P = 0.002

115 % (10/41) of CIMP(+) CRCs vs. 60% (30/46) of CIMP(-) cases (P = 0.002).

116 were measured in the presence and absence of CIMP.

117 bserved in sham mice after administration of CIMP.

118 used univariate and multivariate analyses of CIMP with clinicopathologic variables and tumor mutation

119 appeared to be driven by the associations of CIMP-high cancer with microsatellite instability-high, D

120 that IDH mutation is the molecular basis of CIMP in gliomas, provide a framework for understanding o

121 The underlying cause of CIMP is not known.

122 The causes of CIMP are unknown.

123 and 3 MINT loci (acknowledged classifiers of CIMP) in 344 bladder cancers, 346 head and neck squamous

124 occur almost exclusively as a consequence of CIMP-associated methylation of MLH1.

125 m that MSI cancers arise as a consequence of CIMP.

126 identifying the true cause and definition of CIMP in different forms of human neoplasia.

127 y distinguish disease type, the existence of CIMP and the relative preponderance of hypermethylation

128 However, the existence of CIMP has been challenged.

129 These data suggest that a form of CIMP exists in these solid tumors, although its etiology

130 fer increased plasma and LV tissue levels of CIMP in AVF mice; there was no increase in sham animals.

131 Plasma and LV tissue levels of CIMP were measured by Western analysis.

132 strongly supports the biologic relevance of CIMP in colon cancer.

133 ssation were associated with a lower risk of CIMP-high colorectal cancer, with multivariate hazard ra

134 y (Ptrend = 0.001), but not with the risk of CIMP-low/CIMP-negative cancer (Ptrend = 0.25) (Pheteroge

135 provided novel insight regarding the role of CIMP-specific DNA hypermethylation in gene silencing.

136 tion alterations in CRC, the significance of CIMP status, the development of treatments based on spec

137 rized by DNA hypermethylation of a subset of CIMP-H-associated markers rather than a unique group of

138 us and often result in an underestimation of CIMP frequencies in CRCs.

139 The validity of CIMP, its molecular basis, and its prognostic value rema

140 s involved in, and the mechanistic basis of, CIMP is not understood.

141 the CpG island methylator phenotype (CIMP or CIMP-High) and for the V600E mutation in the BRAF gene.

142 ble (MSS), MSI high or MSI low, CIMP high or CIMP low, CIMP negative, and positive or negative for BR

143 to as 'CpG island methylator phenotype', or 'CIMP'.

144 is bound at the promoters of MLH1 and other CIMP genes, and recruits a corepressor complex that incl

145 bound at the promoters of INK4-ARF and other CIMP genes.

146 lity (MSI), LINE-1 hypomethylation, and p53, CIMP, KRAS and BRAF mutation.

147 se tumors have the hypermethylator phenotype CIMP.

148 ), and the CpG island methylation phenotype (CIMP).

149 ence of the CpG island methylator phenotype (CIMP or CIMP-High) and for the V600E mutation in the BRA

150 ized by the CpG island methylator phenotype (CIMP) (multivariate odds ratio, 2.19; 95% CI, 1.14 to 4.

151 2) have the CpG island methylator phenotype (CIMP) and significantly longer patient survival time tha

152 RCs) have a CpG island methylator phenotype (CIMP) characterized by aberrant DNA hypermethylation and

153 0E]) have a CpG island methylator phenotype (CIMP) characterized by aberrant hypermethylation of many

154 rs with the CpG island methylator phenotype (CIMP) constitute a subset of tumours with extensive epig

155 islands as CpG island methylator phenotype (CIMP) has been described in tumors.

156 ity and the CpG island methylator phenotype (CIMP) in colon cancer.

157 CpG island methylator phenotype (CIMP) in colorectal cancers is characterized by abnormal

158 hway termed CpG island methylator phenotype (CIMP) in CRC, which is characterized by the simultaneous

159 The CpG island methylator phenotype (CIMP) is a newly described mechanism for carcinogenesis

160 The CpG island methylator phenotype (CIMP) is a recently described mechanism for tumorigenesi

161 cancer, the CpG island methylator phenotype (CIMP) is defined as widespread and elevated levels of DN

162 The CpG island methylator phenotype (CIMP) is one of the mechanisms involved in colorectal ca

163 rmethylated CpG island methylator phenotype (CIMP) observed in EBV-associated carcinomas.

164 s) with the CpG island methylator phenotype (CIMP) often associate with epigenetic silencing of hMLH1

165 tability or CpG island methylator phenotype (CIMP) positivity.

166 lthough the CpG island methylator phenotype (CIMP) was first identified and has been most extensively

167 A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papi

168 to have the CpG island methylator phenotype (CIMP), a higher propensity for CpG island DNA methylatio

169 lity (MSI), CpG island methylator phenotype (CIMP), and mutations in BRAF and KRAS.

170 tion, and a CpG island methylator phenotype (CIMP), but precursors are poorly established.

171 oncept of a CpG island methylator phenotype (CIMP), especially in microsatellite stable colon cancer,

172 o status of CpG island methylator phenotype (CIMP), microsatellite instability, v-raf murine sarcoma

173 The CpG island methylator phenotype (CIMP), thoroughly described in colorectal cancer and to

174 guanosine (CpG) island methylator phenotype (CIMP), which appears to be a defining event in approxima

175 type termed CpG island methylator phenotype (CIMP), which includes methylation of such genes as p16 a

176 ized by the CpG island methylator phenotype (CIMP).

177 AS, and the CpG island methylator phenotype (CIMP).

178 display the CpG island methylator phenotype (CIMP).

179 o display a CpG island methylator phenotype (CIMP).

180 (MSI); the CpG island methylator phenotype (CIMP); 18q loss of heterozygosity; KRAS, BRAF, and PIK3C

181 rs have the CpG island methylator phenotype (CIMP+) with methylation and transcriptional silencing of

182 The CpG island methylator phenotype (CIMP-high, CIMP1) is a distinct phenotype associated wit

183 [MSI]-high, CpG island methylator phenotype [CIMP] -positive, positive for BRAF mutation, negative fo

184 displaying CpG island methylator phenotypes (CIMPs), defined as DNA hypermethylation at specific CpG

185 We found that CIMP-positive (CIMP+) tumors convincingly represent a distinct subset,

186 s "CpG island-methylator-phenotype positive (CIMP+)." Two of four carcinomas with microsatellite inst

187 Mice were grouped as follows: sham; sham+CIMP; AVF; and AVF+CIMP (n=6).

188 Compared with sham, CIMP was decreased in AVF mice, and CIMP protein transfe

189 Analysis of transcriptionally silenced CIMP genes in KRAS-positive CRCs indicates that differen

190 Concordant methylation of two or more sites (CIMP-high) was also more frequent in sporadic serrated a

191 s' characterization according to MMR status, CIMP phenotype and TYMS mRNA expression may provide a mo

192 We studied CIMP in hyperplastic polyps (HPs), with emphasis on pati

193 ce of KRAS mutation-associated CIMP subtype (CIMP-low, CIMP2).

194 this mutation was related to poor survival, CIMP high, advanced American Joint Committee on Cancer (

195 nt perspective discusses the use of the term CIMP in cancer, its significance in clinical practice, a

196 vely studied in colorectal cancer, the term "CIMP" has been repeatedly used over the past decade to d

197 We find that CIMP defines two groups of tumors with significantly dif

198 We found that CIMP-positive (CIMP+) tumors convincingly represent a di

199 These observations indicate that CIMP tumors have specific defects in controlling both DN

200 These results suggest that CIMP may be one of the major pathways that contribute to

201 The CIMP phenotype is an early event in gastric cancer, bein

202 Among the CIMP genes are the tumor suppressors p14(ARF), p15(INK4B

203 the majority of these tumors evolve through CIMP.

204 Thus, CIMP is also characterized by more extensive methylation

205 est that there may be a genetic component to CIMP in CRC.

206 on-related carcinogenesis pathway leading to CIMP-high colorectal cancer.

207 unique molecular profile that is similar to CIMP-high, BRAF-mutated colorectal cancers.

208 te analysis of microsatellite stable tumors, CIMP high was related significantly to the V600E BRAF mu

209 rated lesions harbored mutant BRAF, 26% were CIMP-high, and 5% had methylated MLH1.

210 permethylation of hMLH1, and both cases were CIMP+.

211 instability, and all three of the cases were CIMP+.

212 erplastic glands and adenomatous glands were CIMP-high.

213 Sporadic HPs were CIMP-negative (not methylated at any locus), but 43% of

214 le/large HPs, or hyperplastic polyposis were CIMP-high (two or more methylated loci, P = 0.00001).

215 To study whether CIMP is present in gastric cancer, the methylation statu

216 and CIMP inhibits MMP, it is unclear whether CIMP administration attenuates oxidative stress and MMP-

217 BRAF but mutant KRAS may also associate with CIMP in CRC.

218 ic CRCs without CIN would be associated with CIMP.

219 nd SOCS1) were differentially clustered with CIMP-high and CIMP-low according to KRAS and BRAF status

220 d in CIMP(+) CRCs (28/41, 68%) compared with CIMP(-) cases (14/47, 30%, P = 0.0005).

221 Treatment of AVF mice with CIMP significantly abrogated the contractile dysfunction

222 mice and decreased in AVF mice treated with CIMP.

223 mice compared with sham, and treatment with CIMP decreased MMP activity.

224 a panel of colorectal tumors with or without CIMP.