scholarly journals BRAF mutation, CpG island methylator phenotype and microsatellite instability occur more frequently and concordantly in mucinous than non-mucinous colorectal cancer

2006 ◽  
Vol 118 (11) ◽  
pp. 2765-2771 ◽  
Author(s):  
Hirofumi Tanaka ◽  
Guoren Deng ◽  
Koji Matsuzaki ◽  
Sanjay Kakar ◽  
Grace E. Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Braf Mutation ◽  
Cpg Island ◽  
Cpg Island Methylator Phenotype ◽  
Methylator Phenotype

CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer

2006 ◽  
Vol 38 (7) ◽  
pp. 787-793 ◽  
Author(s):  
Daniel J Weisenberger ◽  
Kimberly D Siegmund ◽  
Mihaela Campan ◽  
Joanne Young ◽  
Tiffany I Long ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Braf Mutation ◽  
Cpg Island ◽  
Cpg Island Methylator Phenotype ◽  
Methylator Phenotype

Clinicopathologic Characteristics, CpG Island Methylator Phenotype, and BRAF Mutations in Microsatellite-Stable Colorectal Cancers Without Chromosomal Instability

2008 ◽  
Vol 132 (6) ◽  
pp. 958-964
Author(s):  
Sanjay Kakar ◽  
Guoren Deng ◽  
Vaibhav Sahai ◽  
Koji Matsuzaki ◽  
Hirofumi Tanaka ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Braf Mutation ◽  
Chromosomal Instability ◽  
Cpg Island ◽  
Adverse Outcomes ◽  
Colorectal Carcinogenesis ◽  
Cpg Island Methylator Phenotype ◽  
Braf Mutations ◽  
Methylator Phenotype

Abstract Context.—The 2 chief pathways implicated in colorectal carcinogenesis, microsatellite instability and chromosomal instability, are not present in 20% to 37% of cases. Objective.—To determine whether the CpG island methylator phenotype (CIMP) pathway, characterized by simultaneous methylation of several known tumor suppressor genes, is the principal underlying mechanism in cases without chromosomal or microsatellite instability, and to determine the significance of CIMP pathway and BRAF mutations in microsatellite-stable (MSS) cases. Design.—Clinicopathologic features and chromosomal instability status by loss of heterozygosity analysis were determined in 83 cases of colorectal cancer in which microsatellite instability, CIMP status, BRAF mutations, and KRAS mutations were previously known. Results.—Microsatellite instability was present in 14 cases (17%). Of the 69 MSS cases (83%), chromosomal instability manifested by LOH involving at least one locus was observed in 53 cases (64%). Hence, 16 (19%) of 83 colorectal cancer cases showed neither microsatellite instability nor chromosomal instability. These cases had a low incidence of CIMP (3/16; 19%) and BRAF mutation (1/16; 6%). The 5-year survival in these cases was significantly better compared with MSS cases with chromosomal instability (80% vs 54%, P = .02). BRAF mutations were identified in 10 MSS cases (15%). BRAF mutation in MSS cases correlated significantly with high-level chromosomal instability (P = .009) and poor 5-year survival (0% vs 70%, P < .001). Conclusions.—CIMP does not appear to play a key role in colorectal cancer without microsatellite instability and chromosomal instability. These cases have a better survival, probably related to absence of significant chromosomal instability. BRAF mutations in MSS cases are associated with high levels of chromosomal instability that are likely responsible for the adverse outcomes in these cases.

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

TGFBR2 mutation is correlated with CpG island methylator phenotype in microsatellite instability-high colorectal cancer

2007 ◽  
Vol 38 (4) ◽  
pp. 614-620 ◽  
Author(s):  
Shuji Ogino ◽  
Takako Kawasaki ◽  
Akiyo Ogawa ◽  
Gregory J. Kirkner ◽  
Massimo Loda ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Cpg Island ◽  
Cpg Island Methylator Phenotype ◽  
Methylator Phenotype

CpG Island Methylator Phenotype in Colorectal Cancers: Comparison of the New and Classic CpG Island Methylator Phenotype Marker Panels

2008 ◽  
Vol 132 (10) ◽  
pp. 1657-1665 ◽  
Author(s):  
Sun Lee ◽  
Nam-Yun Cho ◽  
Eun Joo Yoo ◽  
Jung Ho Kim ◽  
Gyeong Hoon Kang
Keyword(s):  
Clinical Outcome ◽  
Microsatellite Instability ◽  
Braf Mutation ◽  
Cpg Island ◽  
Tumor Location ◽  
Colorectal Cancers ◽  
Clinicopathologic Features ◽  
Cpg Island Methylator Phenotype ◽  
P Values ◽  
Methylator Phenotype

Abstract Context.—CpG island methylator phenotype (CIMP) designates a subset of colorectal cancers featuring concordant hypermethylation of multiple promoter CpG islands. Little is known about the clinical outcome or histologic characteristics of CIMP-positive colorectal cancers defined by recently identified CpG island methylator phenotype panels. Objective.—To investigate and compare the molecular and clinicopathologic features of CIMP-positive colorectal cancers defined by classic (p16, hMLH1, MINT1, MINT2, MINT31) and new (CACNA1G, IGF2, NEUROG1, RUNX3, SOCS1) CIMP panels. Design.—We analyzed 130 colorectal cancers for hypermethylation of both panels using methylation-specific polymerase chain reaction. Results.—With at least 2 markers methylated, both classic (39/130; 23.1%) and new (23.1%) CIMP-positive colorectal cancers were significantly associated with proximal tumor location, microsatellite instability, and BRAF mutation (all P values were less than .05). The new panel outperformed the classic panel in detecting these features. With at least 3 markers methylated, new CIMP-positive colorectal cancers (16.9%) were closely associated with proximal tumor location, low frequency of KRAS mutation, and high frequency of BRAF mutation (all P values were less than .05), whereas classic CIMP-positive colorectal cancers (18.5%) were closely associated with proximal tumor location, frequent microsatellite instability, and frequent BRAF mutation (all P values were less than .05). Analyzing a combination of CIMP and microsatellite instability status, CIMP-positive/microsatellite instability–negative colorectal cancers had the worst clinical outcomes. Conclusions.—Whereas the classic panel outperformed in predicting clinical outcome, the new panel was superior in detecting known clinicopathologic features of CIMP but inferior in prognostication power.

scholarly journals CpG island methylator phenotype, microsatellite instability, BRAF mutation and clinical outcome in colon cancer

Gut ◽  
2008 ◽  
Vol 58 (1) ◽  
pp. 90-96 ◽  
Author(s):  
S. Ogino ◽  
K. Nosho ◽  
G. J Kirkner ◽  
T. Kawasaki ◽  
J. A Meyerhardt ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Clinical Outcome ◽  
Microsatellite Instability ◽  
Braf Mutation ◽  
Cpg Island ◽  
Cpg Island Methylator Phenotype ◽  
Methylator Phenotype
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