scholarly journals CpG Island Methylator Phenotype-Low (CIMP-Low) in Colorectal Cancer: Possible Associations with Male Sex and KRAS Mutations

2006 ◽  
Vol 8 (5) ◽  
pp. 582-588 ◽  
Author(s):  
Shuji Ogino ◽  
Takako Kawasaki ◽  
Gregory J. Kirkner ◽  
Massimo Loda ◽  
Charles S. Fuchs
Keyword(s):  
Colorectal Cancer ◽  
Cpg Island ◽  
Cpg Island Methylator Phenotype ◽  
Kras Mutations ◽  
Male Sex ◽  
Methylator Phenotype

scholarly journals Clinicopathological and Molecular Profiles of Sporadic Microsatellite Unstable Colorectal Cancer with or without the CpG Island Methylator Phenotype (CIMP)

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3487
Author(s):  
Shih-Ching Chang ◽  
Anna Fen-Yau Li ◽  
Pei-Ching Lin ◽  
Chun-Chi Lin ◽  
Hung-Hsin Lin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cpg Island ◽  
Gene Mutations ◽  
Proximal Colon ◽  
Tnm Stage ◽  
Cpg Island Methylator Phenotype ◽  
Kras Mutations ◽  
Methylator Phenotype ◽  
Next Generation Sequencing Ngs ◽  
Mutation Spectra

Background: The 5’-C-phosphate-G-3’ island methylator phenotype (CIMP) is a specific phenotype of colorectal cancer (CRC) associated with microsatellite instability-high (MSI-high) tumors. Methods: In this study, we determined the CIMP status using eight methylation markers in 92 MSI-high CRC patients after excluding five germline mismatch repair (MMR) gene mutations analyzed by next-generation sequencing (NGS) and confirmed by Sanger sequencing. The mutation spectra of 22 common CRC-associated genes were analyzed by NGS. Results: Of the 92 sporadic MSI-high tumors, 23 (25%) were considered CIMP-high (expressed more than 5 of 8 markers). CIMP-high tumors showed proximal colon preponderance and female predominance. The mutation profiles of CIMP-high tumors were significantly different from those of CIMP-low or CIMP-0 tumors (i.e., higher frequencies of BRAF, POLD1, MSH3, and SMAD4 mutations but lower frequencies of APC, TP53, and KRAS mutations). Multivariate analysis demonstrated that tumor, node, metastasis (TNM) stage was the independent prognostic factor affecting overall survival (OS). Among the MSI-high cases, the CIMP status did not impact the outcome of patients with MSI-high tumors. Conclusions: Only TNM stage was a statistically significant predictor of outcomes independent of CIMP profiles in MSI-high CRC patients. Sporadic MSI-high CRCs with different mechanisms of carcinogenesis have specific mutation profiles and clinicopathological features.

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 The Role of the CpG Island Methylator Phenotype in Colorectal Cancer Prognosis Depends on Microsatellite Instability Screening Status

2010 ◽  
Vol 16 (6) ◽  
pp. 1845-1855 ◽  
Author(s):  
Anna M. Dahlin ◽  
Richard Palmqvist ◽  
Maria L. Henriksson ◽  
Maria Jacobsson ◽  
Vincy Eklöf ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Cpg Island ◽  
Cancer Prognosis ◽  
Cpg Island Methylator Phenotype ◽  
Methylator Phenotype

scholarly journals IGFBP7 is a p53-responsive gene specifically silenced in colorectal cancer with CpG island methylator phenotype

2009 ◽  
Vol 31 (3) ◽  
pp. 342-349 ◽  
Author(s):  
Hiromu Suzuki ◽  
Shinichi Igarashi ◽  
Masanori Nojima ◽  
Reo Maruyama ◽  
Eiichiro Yamamoto ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cpg Island ◽  
Cpg Island Methylator Phenotype ◽  
Responsive Gene ◽  
Methylator Phenotype

Determination & expression of chimeric protein in colorectal cancer: A bioinformatics Approach

2021 ◽  
Vol 2 (3) ◽  
pp. 35-67
Author(s):  
Gargi Bhattacharyya ◽  
Amit Chattopadhay
Keyword(s):  
Colorectal Cancer ◽  
Cpg Island ◽  
Therapeutic Process ◽  
Chimeric Protein ◽  
Ageing Population ◽  
Cpg Island Methylator Phenotype ◽  
High Risk Factors ◽  
Bowel Movements ◽  
Methylator Phenotype ◽  
New Treatments

Colorectal cancer (CRC) accounts for about 10% of cancer-related mortality in western countries. Increasing ageing population, undesirable modern dietary and high-risk factors like smoking, obesity and low exercise. Chromosomal instability (CIN), CpG island methylator phenotype (CIMP), and microsatellite instability are the three different mechanism that give rise to CRC. It often grow slowly, and customarily doesn’t produce symptoms until reaching a substantial size of several centimeters, which can block the passage of feces and cause cramping, pain, or bleeding which can present as visible bleeding with bowel movements or, rarely, dark “tarry” stools. Most colon tumors develop via a several different processes involving a series of histological, morphological, and genetical changes that accumulate over time to time. New treatments for primary and metastatic colorectal cancer have emerged, like in variety of therapeutic process by preparing chimeric proteins that triggers the cells and stop it from getting severe.

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.

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