title: The methylator phenotype in microsatellite stable colorectal cancers is characterized by a distinct gene expression profile.
abstract: The CpG island methylator phenotype (CIMP) in colorectal tumours can be recognized by an increased frequency of aberrant methylation in a specific set of genomic loci. Because of the strong association of CIMP with high microsatellite instability (MSI-H), the identification of CIMP+ tumours within microsatellite stable (MSS) colorectal cancers may not be straightforward. To overcome this potential limitation, we have built an improved seven-locus set of methylation markers that includes CACNA1G, IGF2, RUNX3, HTR6, RIZ1, MINT31, and MAP1B. This new set of CIMP markers revealed a bimodal distribution of methylation frequencies in a group of 95 MSS colorectal cancers, which allowed a clearer separation between CIMP classes. Correlation of MSS CIMP+ tumours with bio-pathological traits revealed significant associations with location to the proximal colon, mucinous histology, BRAF mutation, and chromosomal stability. A potential trend towards an adverse prognosis of CIMP+ cases was associated with the high frequency of BRAF mutations present within this cohort of tumours. Microarray analysis revealed that CIMP+ tumours are characterized by a unique expression profile, a result that confirms that CIMP+ tumours represent a truly distinct molecular class within MSS colorectal cancers.
authors.affiliation: Dipartimento di Medicina Sperimentale e Diagnostica, Università di Ferrara, via Luigi Borsari 46, 44100 Ferrara, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Ferracin
authors.forename: R
authors.initials: R
authors.lastname: Gafà
authors.forename: E
authors.initials: E
authors.lastname: Miotto
authors.forename: A
authors.initials: A
authors.lastname: Veronese
authors.forename: C
authors.initials: C
authors.lastname: Pultrone
authors.forename: S
authors.initials: S
authors.lastname: Sabbioni
authors.forename: G
authors.initials: G
authors.lastname: Lanza
authors.forename: M
authors.initials: M
authors.lastname: Negrini
mesh_terms: D000368:Aged; D016000:Cluster Analysis; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D005819:Genetic Markers; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats / Q000235:genetics*; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010641:Phenotype; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; D005819:Genetic Markers; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf