CpG island methylated phenotype

Goel A, Nagasaka T, Arnold CN et al. The CpG island methylator phenotype and chromosomal instability are inversely correlated in sporadic colorectal cancer. Gastroenterology 2007 132 127-138. Swanton C, Tomlinson 1, Downward J. Chromosomal instability, colorectal cancer and taxane resistance. CeZ/Cyc/e 2006 5 818-823. 

Ogino S, Kawasaki T, Nosho K, et al. LINE-1 hypomethylation is inversely associated with microsatellite instability and CpG island methylator phenotype in colorectal cancer. Int J Cancer. 2008 122 2767-2773. 

Eew studies have been done on the molecular features of gastrointestinal endocrine tumors. Allelic loss of llq has been detected in GI endocrine tumors associated with MENl, and LOH of 1 Iq is also present in a subset of sporadic GI endocrine tumors. Mutations of the MENl gene are present in approximately 30% of sporadic gastrinomas and in occasional midgut and hindgut endocrine tumors. In contrast to pancreatic endocrine tumors, the CpG island methylator phenotype is frequent in GI endocrine tumors. Beta-catenin exon 3 mutations are relatively common (38%) in these tumors, and up to 80% of the tumors show nuclear and cytoplasmic localization of the corresponding protein. Other studies, however, reported absence of exon 3 mutations, but nuclear f5-catenin was found in 30% of cases. In contrast, extra-GI endocrine tumors were negative for nuclear f5-catenin. 

MSI-H/mismatch repair protein-deficient colorectal cancers, evaluated by either MSI testing or IHC, may have a better survival in subsets of colon cancer patients. This effect may be related to the CpG island methylator phenotype (widespread promoter methyla-tion). MSI-H tumors may also respond differently to... 

Ogino, S., Kawasaki, T., Ogawa, A., Kirkner, G. J., Loda, M. and Fuchs, C. S., Fatty acid synthase overexpression in colorectal cancer is associated with microsatellite instability, independent of CpG island methylator phenotype. Hum Pathol 38 (2007) 842-849. 

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