Abstract 4909: The role of CpG island methylator phenotype 2 (CIMP2) in early onset colorectal cancer patients

CpG Island Methylator Phenotype (CIMP), characterized by methylation at various promoter sites, has been reported as a subgroup in colorectal cancer. CIMP1 is often associated with microsatellite instability (MSI) as well as BRAF mutation while CIMP negative enriched with P53 mutant. Besides, a CIMP2 classification has also been established and indicated to be associated with KRAS mutation. Most of these experiments related to CIMP were carried out on tumor samples from late onset patients with a mean or median age of at least 60. Thus it was of interest to observe any deviation of such pattern among early onset colorectal cancer population. Bisulfite conversion of the extracted DNA from 73 tumor samples with MSS status were examined via pyrosequence for their methylation status among loci MINT1, MINT2 and MINT27, the most frequently methylated sites reported in CIMP 2 phenomenon. These samples were free from MLH1 methylation and BRAF mutation to exclude conditions of CIMP1. The age group ranged from 29 to 68 years old with a mean age of 50.7 years old. Sequencing of its genomic DNA for KRas mutation was also screened as per se to previous studies. It was found that CIMP2 appeared more frequently in patients over the age of 50 (p=0.04) when compared with patients below 50 years old. Furthermore, methylation of the CIMP 2 loci examined (MINT1, MINT2 and MINT27) were most likely accompanied with the mutation of KRas in patients over 50 years old (p=0.05) while there was no observed correlation of CIMP 2 loci and KRas mutation in patient samples under 50 years of age. Since the CIMP2 phenotype is not seen in early-onset CRC samples, our data suggests that an alternative pathway, but not CIMP, may be responsible for the tumorigenesis of early-onset MSS CRC. Moreover, current studies proposed chromosomal instability may be a distinct mechanism in the pathogenesis of CRC, thus investigation would be carried on this aspect. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4909.