title: The CpG island methylator phenotype in colorectal cancer: progress and problems.
abstract: In recent years, attention has focused on the biology and potential clinical importance of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC). While it is generally well accepted that etiologically and clinically distinct subgroups exist in this disease, a precise definition of CIMP remains to be established. Here, we summarize existing literature that documents the prevalence of CIMP in CRC, with particular attention to the various methods and definitions used to classify a tumor as CIMP positive. Through a systematic review on both case-series and population based studies, we examined only original research articles reporting on sporadic CRC and/or adenomas in unselected cases. Forty-eight papers published between January 1999 and August 2011 met the inclusion criteria. We describe the use of multiple gene panels, marker threshold values, and laboratory techniques which results in a wide range in the prevalence of CIMP. Because there is no universal standard or consensus on quantifying the phenotype, establishing its true prevalence is a challenge. This bottleneck is becoming increasingly evident as molecular pathological epidemiology continues to offer possibilities for clear answers regarding environmental risk factors and disease trends. For the first time, large, unselected series of cases are available for analysis, but comparing populations and pooling data will remain a challenge unless a universal definition of CIMP and a consensus on analysis can be reached, and the primary cause of CIMP identified.
authors: Dept. of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, 6200MD Maastricht, the Netherlands.
authors: Laura A E
authors: LA
authors: Hughes
authors: Carolina A J
authors: CA
authors: Khalid-de Bakker
authors: Kim M
authors: KM
authors: Smits
authors: Piet A
authors: PA
authors: van den Brandt
authors: Daisy
authors: D
authors: Jonkers
authors: Nita
authors: N
authors: Ahuja
authors: James G
authors: JG
authors: Herman
authors: Matty P
authors: MP
authors: Weijenberg
authors: Manon
authors: M
authors: van Engeland
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D017408:Guidelines as Topic; D006801:Humans; D010641:Phenotype