The methylator phenotype in microsatellite stable colorectal cancers is characterized by a distinct gene expression profile |
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Authors: | Ferracin M Gafà R Miotto E Veronese A Pultrone C Sabbioni S Lanza G Negrini M |
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Affiliation: | Dipartimento di Medicina Sperimentale e Diagnostica, Università di Ferrara, via Luigi Borsari 46, 44100 Ferrara, Italy. |
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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. |
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Keywords: | colorectal cancer methylator phenotype CIMP microsatellite instability microarray |
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