Miroslav Svoboda

MicroRNAs and Rectal Cancer

Spontaneous rectal cancers usually arise as a consequence of somatic mutation of the APC gene followed by other mutations (K-ras mutation, DCC inactivation and p53 gene mutation), well-known today as the adenoma-to-carcinoma sequence (Kinzler & Vogelstein, 1996). This sequence covers most spontaneous rectal cancers (80%). However mutation(s) in DNA repair genes; the MSH1, MSH2, PMS1, PMS2 are also involved in certain fraction of rectal tumours, leading to microsatellite instability (Kim et al., 2006). Today about seventy different mutations, including important oncogenes and tumour suppressor genes, are known to be present in various colorectal cancers (Sjoblom, 2008). Colorectal cancers also exhibit changes in DNA methylation with hypermethylation of CpG islands and hypomethylation of oncogenes (Kang, 2007). The mutated cancer genotype is associated with changed expression in many genes, as has been demonstrated by powerful microarray analysis and Real Time PCR technology. It is now well known that mutations and changed DNA methylation pattern, as well as changes of mRNA transcription, are accompanied by changes of expression in certain microRNAs.