scholarly journals CpG Island Methylator Phenotype and Prognosis of Colorectal Cancer in Northeast China

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Xia Li ◽  
Fulan Hu ◽  
Yibaina Wang ◽  
Xiaoping Yao ◽  
Zuoming Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Promoter Methylation ◽  
Northeast China ◽  
Proportional Hazards ◽  
Cpg Island ◽  
Sporadic Colorectal Cancer ◽  
Cpg Island Methylator Phenotype ◽  
Methylator Phenotype ◽  
Worse Prognosis

Purpose. To investigate the association between CpG island methylator phenotype (CIMP) and the overall survival of sporadic colorectal cancer (CRC) in Northeast China.Methods. 282 sporadic CRC patients were recruited in this study. We selectedMLH1,MGMT,p16,APC,MINT1,MINT31, andRUNX3as the CIMP panel markers. The promoter methylation was assessed by methylation sensitive high resolution melting (MS-HRM). Proportional hazards-regression models were fitted with computing hazard ratios (HR) and the corresponding 95% confidence intervals (95% CI).Results. 12.77% (36/282) of patients were CIMP-0, 74.1% (209/282) of patients were CIMP-L, and 13.12% (37/282) of patients were CIMP-H. The five-year survival of the 282 CRC patients was 58%. There was significant association betweenAPCgene promoter methylation and CRC overall survival (HR = 1.61; 95% CI: 1.05–2.46;P=0.03). CIMP-H was significantly associated with worse prognosis compared to CIMP-0 (HR = 3.06; 95% CI: 1.19–7.89;P=0.02) and CIMP-L (HR = 1.97; 95% CI: 1.11–3.48;P=0.02), respectively. While comparing with the combine of CIMP-L and CIMP-0 (CIMP-L/0), CIMP-H also presented a worse prognosis (HR = 2.31; 95% CI: 1.02–5.24;P=0.04).Conclusion. CIMP-H may be a predictor of a poor prognosis of CRC in Northeast China patients.

scholarly journals How theBRAFV600E Mutation Defines a Distinct Subgroup of Colorectal Cancer: Molecular and Clinical Implications

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Catherine E. Bond ◽  
Vicki L. J. Whitehall
Keyword(s):  
Colorectal Cancer ◽  
Cpg Island ◽  
Early Event ◽  
Sporadic Colorectal Cancer ◽  
Cpg Island Methylator Phenotype ◽  
Distinct Subgroup ◽  
Molecular Features ◽  
Map Kinase Pathway ◽  
Methylator Phenotype ◽  
Kinase Pathway

TheBRAFoncogene is an integral component of the MAP kinase pathway, and an activating V600E mutation occurs in 15% of sporadic colorectal cancer. This is an early event in serrated pathway tumourigenesis, and theBRAFV600E has been commonly associated with the CpG island methylator phenotype, microsatellite instability (MSI), and a consistent clinical presentation including a proximal location and predilection for elderly females. A proportion of theBRAFmutant lesions remain as microsatellite stable (MSS), and in contrast to the MSI cancers, they have an aggressive phenotype and correlate with poor patient outcomes. Recent studies have found that they have clinical and molecular features of both theBRAFmutant/MSI and the conventionalBRAFwild-type cancers and comprise a distinct colorectal cancer subgroup. This review highlights the importance of theBRAFmutation occurring in colorectal cancer stratified for molecular background and discusses its prognostic and clinical significance.

CpG Island Methylator Phenotype May Predict Poor Overall Survival of Patients with Stage IV Colorectal Cancer

Oncology ◽  
2018 ◽  
Vol 96 (3) ◽  
pp. 156-163
Author(s):  
Kuo-Hsing  Chen ◽  
Liang-In  Lin ◽  
Li-Hui  Tseng ◽  
Yu-Lin Lin ◽  
Jau-Yu Liau ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cpg Island ◽  
Stage Iv ◽  
Cpg Island Methylator Phenotype ◽  
Poor Overall Survival ◽  
Stage Iv Colorectal Cancer ◽  
Methylator Phenotype

scholarly journals Polymorphisms in methyl-group metabolism genes and risk of sporadic colorectal cancer with relation to the CpG island methylator phenotype

2010 ◽  
Vol 34 (3) ◽  
pp. 338-344 ◽  
Author(s):  
Pawel Karpinski ◽  
Aleksander Myszka ◽  
David Ramsey ◽  
Blazej Misiak ◽  
Justyna Gil ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cpg Island ◽  
Sporadic Colorectal Cancer ◽  
Cpg Island Methylator Phenotype ◽  
Methyl Group ◽  
Methylator Phenotype

scholarly journals IGFBP3 Promoter Methylation in Colorectal Cancer: Relationship with Microsatellite Instability, CpG Island Methylator Phenotype, p53

Neoplasia ◽  
2007 ◽  
Vol 9 (12) ◽  
pp. 1091-1098 ◽  
Author(s):  
Takako Kawasaki ◽  
Katsuhiko Nosho ◽  
Mutsuko Ohnishi ◽  
Yuko Suemoto ◽  
Gregory J. Kirkner ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Promoter Methylation ◽  
Cpg Island ◽  
Cpg Island Methylator Phenotype ◽  
Methylator Phenotype

scholarly journals Characterization of Chilean patients with sporadic colorectal cancer according to the three main carcinogenic pathways: Microsatellite instability, CpG island methylator phenotype and Chromosomal instability

Tumor Biology ◽  
2020 ◽  
Vol 42 (7) ◽  
pp. 101042832093849 ◽  
Author(s):  
Ana María Wielandt ◽  
Claudia Hurtado ◽  
Mauricio Moreno C ◽  
Cynthia Villarroel ◽  
Magdalena Castro ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Latin American ◽  
Chromosomal Instability ◽  
Cpg Island ◽  
Sporadic Colorectal Cancer ◽  
Cpg Island Methylator Phenotype ◽  
Kras Mutations ◽  
Group 3 ◽  
Methylator Phenotype ◽  
Chilean Population

Molecular classification of colorectal cancer is difficult to implement in clinical settings where hundreds of genes are involved, and resources are limited. This study aims to characterize the molecular subtypes of patients with sporadic colorectal cancer based on the three main carcinogenic pathways microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and chromosomal instability (CIN) in a Chilean population. Although several reports have characterized colorectal cancer, most do not represent Latin-American populations. Our study includes 103 colorectal cancer patients who underwent surgery, without neoadjuvant treatment, in a private hospital between 2008 and 2017. MSI, CIN, and CIMP status were assessed. Frequent mutations in KRAS, BRAF, and PIK3CA genes were analyzed by Sanger sequencing, and statistical analysis was performed by Fisher’s exact and/or chi-square test. Survival curves were estimated with Kaplan–Meier and log-rank test. Based on our observations, we can classify the tumors in four subgroups, Group 1: MSI-high tumors (15%) are located in the right colon, occur at older age, and 60% show a BRAF mutation; Group 2: CIN-high tumors (38%) are in the left colon, and 26% have KRAS mutations. Group 3: [MSI/CIN/CIMP]-low/negative tumors (30%) are left-sided, and 39% have KRAS mutations; Group 4: CIMP-high tumors (15%) were more frequent in men and left side colon, with 27% KRAS and 7% presented BRAF mutations. Three percent of patients could not be classified. We found that CIMP-high was associated with a worse prognosis, both in MSI-high and MSI stable patients (p = 0.0452). Group 3 (Low/negative tumors) tend to have better overall survival compared with MSI-high, CIMP-high, and CIN-high tumors. This study contributes to understanding the heterogeneity of tumors in the Chilean population being one of the few characterizations performed in Latin-America. Given the limited resources of these countries, these results allow to improve molecular characterization in Latin-American colorectal cancer populations and confirm the possibility of using the three main carcinogenic pathways to define therapeutic strategies.

scholarly journals Comprehensive analysis of the MLH1 promoter region in 480 patients with colorectal cancer and 1150 controls reveals new variants including one with a heritable constitutional MLH1 epimutation

2018 ◽  
Vol 55 (4) ◽  
pp. 240-248 ◽  
Author(s):  
Monika Morak ◽  
Ayseguel Ibisler ◽  
Gisela Keller ◽  
Ellen Jessen ◽  
Andreas Laner ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Promoter Methylation ◽  
Transcriptional Repression ◽  
De Novo ◽  
Cpg Island ◽  
Promoter Sequence ◽  
Cpg Island Methylator Phenotype ◽  
Allele Specific ◽  
Methylator Phenotype

BackgroundGermline defects in MLH1, MSH2, MSH6 and PMS2 predisposing for Lynch syndrome (LS) are mainly based on sequence changes, whereas a constitutional epimutation of MLH1(CEM) is exceptionally rare. This abnormal MLH1 promoter methylation is not hereditary when arising de novo, whereas a stably heritable and variant-induced CEM was described for one single allele. We searched for MLH1 promoter variants causing a germline or somatic methylation induction or transcriptional repression.MethodsWe analysed the MLH1 promoter sequence in five different patient groups with colorectal cancer (CRC) (n=480) composed of patients with i) CEM (n=16), ii) unsolved loss of MLH1 expression in CRC (n=37), iii) CpG-island methylator-phenotype CRC (n=102), iv) patients with LS (n=83) and v) MLH1-proficient CRC (n=242) as controls. 1150 patients with non-LS tumours also served as controls to correctly judge the results.ResultsWe detected 10 rare MLH1 promoter variants. One novel, complex MLH1 variant c.-63_-58delins18 is present in a patient with CRC with CEM and his sister, both showing a complete allele-specific promoter methylation and transcriptional silencing. The other nine promoter variants detected in 17 individuals were not associated with methylation. For four of these, a normal, biallelic MLH1 expression was found in the patients' cDNA.ConclusionWe report the second promoter variant stably inducing a hereditary CEM. Concerning the classification of promoter variants, we discuss contradictory results from the literature for two variants, describe classification discrepancies between existing rules for five variants, suggest the (re-)classification of five promoter variants to (likely) benign and regard four variants as functionally unclear.

scholarly journals The CpG Island Methylator Phenotype and Chromosomal Instability Are Inversely Correlated in Sporadic Colorectal Cancer

2007 ◽  
Vol 132 (1) ◽  
pp. 127-138 ◽  
Author(s):  
Ajay Goel ◽  
Takeshi Nagasaka ◽  
Christian N. Arnold ◽  
Toru Inoue ◽  
Cody Hamilton ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Chromosomal Instability ◽  
Cpg Island ◽  
Sporadic Colorectal Cancer ◽  
Cpg Island Methylator Phenotype ◽  
Methylator Phenotype
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