Tumor and adjacent mucosal tissues were homoge nized by MagNA Lyser.

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Tumor and adjacent mucosal tissues were homoge nized by MagNA Lyser.

Post  jy9202 on Fri Mar 20, 2015 7:03 am

DNA hypomethylation, prevalent as a genome wide event, usually occurs in more advanced stages of tumor development whereas DNA hypermethylation is often observed as a discrete, targeted event within tumor cells, resulting in specific loss of gene expression. Based on a number of relatively large case control and prospective cohort studies, [You must be registered and logged in to see this link.] ∼30 40% of sporadic proximal site colon cancers are CIMP positive, compared to 3 12% of distal colon and rectal cancers. Thus, CIMP is at tributable to tumors of the proximal colon, independently of MSI status. CIMP has been also associated with BRAF mutations in both microsatellite stable and unstable colon cancers. It has been suggested that there are two general types of CIMP in sporadic tumors CIMP high, re lated to BRAF mutations and MLH1 methylation, and CIMP low, related to KRAS mutations.

Approximately 90% of all MMR alterations modifications in sporadic CRC cases are most commonly caused by epi genetic inactivation of MLH1 or MSH2 gene. The hypermethylation of the MLH1 promoter is also the pre dominant cause of MSI high in sporadic tumors. MSI H cancers with methylated MLH1 are distinct from the rest of CRC by delayed onset and association with the female gender. [You must be registered and logged in to see this link.] On the other hand, CRC cases without altered MMR genes show low frequency MSI or are microsatellite stable. Moreover, gene alterations of other MMR genes may also be involved in the CRC progression. Goel et al. assumed that germline hypermethylation of MLH1 and MSH2 may serve as predisposing events in some CRC cases.

The Czech Republic has one of the highest reported inci dences of CRC worldwide, thus the analysis of mRNA expression profile of MMR genes and their epigenetic characterization [You must be registered and logged in to see this link.] has a great meaning. Apparently, the clari fication of a potentially abnormal epigenetic profile of tumor tissues, as well as their genetic constitution, could contribute to better classify the CRC cases or could ultim ately result in the improvement of therapy. Thus the aim of our study was to investigate the epi genetic characteristics and gene expression profiling of MMR genes in tumors of CRC patients of Czech nation ality, with respect to their clinical and histopathological characteristics. We have hypothesized that the high inci dence of CRC in this country could be due to different genetic and epigenetic pattern of DNA repair genes, which could reflect possible specific geographical, ethnic, dietary or lifestyle factors.

Methods Patients characteristics and collection of biological specimen Fifty three patients with sporadic CRC were recruited be tween 2009 and 2011 at the Thomayer Hospital and at the General University Hospital, where they underwent surgical resection. All pa tients signed an informed consent. Ethics approval was granted by the committees of the above hospitals. From each patient, tumor tissue and adjacent mucosal colon rectal tissue were resected and deep frozen immediately after removal. Per ipheral blood was taken a day before surgery and stored at 4 C until processing that was no longer than 3 hours. The clinical stage of patients at diagnosis was classified accord ing to the tumor node metastasis system accord ing to UICC.

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