scholarly journals Retrotransposon insertions can initiate colorectal cancer and are associated with poor survival

2018 ◽  
Author(s):  
Tatiana Cajuso ◽  
Päivi Sulo ◽  
Tomas Tanskanen ◽  
Riku Katainen ◽  
Aurora Taira ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Allelic Imbalance ◽  
Cpg Island ◽  
Colorectal Carcinogenesis ◽  
Cancer Genes ◽  
Cpg Island Methylator Phenotype ◽  
Whole Genomes ◽  
Methylator Phenotype ◽  
Retrotransposon Activity

Genomic instability pathways in colorectal cancer (CRC) have been extensively studied, but the role of retrotransposition in colorectal carcinogenesis remains poorly understood. Although retrotransposons are usually repressed, they become active in several human cancers, in particular those of the gastrointestinal tract. Here we characterize retrotransposon insertions in 202 colorectal tumor whole genomes and investigate their associations with molecular and clinical characteristics. We found highly variable retrotransposon activity among tumors and identified recurrent insertions in 15 known cancer genes. In approximately 1% of the cases we identified insertions in APC, likely to be tumor-initiating events. Insertions were positively associated with the CpG island methylator phenotype and the genomic fraction of allelic imbalance. Clinically, high number of insertions was independently associated with poor disease-specific survival.

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

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.

The prognostic role of CpG island methylator phenotype in metastatic colorectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 667-667
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 ◽  
Rank Test ◽  
Prognostic Role ◽  
Cpg Island Methylator Phenotype ◽  
Poor Prognostic Factor ◽  
Significant Difference ◽  
Methylator Phenotype

667 Background: The prognostic role of CpG Island Methylator Phenotype (CIMP) in colorectal cancer (CRC) is still controversial, especially in metastatic CRC. Methods: We retrospectively analyzed the CpG island methylator phenotype (CIMP) in stage I to IV CRC specimens, which were diagnosed during 2005-2013. CIMP status was determined using a 5- gene MethyLight-based assay ( p16, MINT1, MINT2, MINT31, and MLH1). Tumors were designated as CIMP if 3 or more of 5 genes gave percent of methylated reference value ≧ 10. The clinicopatholoical characteristics, anti-cancer therapies, and the overall survival outcome were reviewed. Overall survival (OS) was compared between patients with CIMP CRC and those with non-CIMP CRC. Results: Among 450 patients with successfully determined CIMP status, 259 (57.56%) were male, 312 (70.31%) were stages I-III, 316 (70.69%) were left-sided CRC. In the survival analyses in stages I-IV patients, there was no significant difference in OS between those with or without CIMP (long rank test, p = 0.4526). Importantly, patients with metastatic CIMP CRC had poor OS than those with metastatic non-CIMP CRC (median survival, CIMP vs. non-CIMP: 1.36 vs. 3.11 years, log rank test, p = 0.0047). In a multivariate analysis, which adjusted prognostic variables such as: KRAS and BRAF mutations, microsatellite instability status, age, sex, grade, primary site, metastatic site number, chemotherapies and targeted therapies, CIMP remained an independent poor prognostic factor for OS (HR = 6.213, 95% confidence interval: 2.443 to 15.799, p = 0.0001) in metastatic CRC. In an exploratory analysis, there were more tumors with liver metastases at diagnosis in CIMP CRC than in non-CIMP CRC (94.4% vs. 71.3%, p = 0.0416). Conclusions: Our data demonstrated CIMP might independently predict poor survival in metastatic CRC in a large East Asian cohort.

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 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
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