Colorectal carcinoma (CRC) arises as a result of accumulation of different types of genome damages: transcription disorders of genes and epigenetic disorders. Among the genetic disorders, chromosomal instability (CIN) and microsatellite instability (MSI) are of major importance. Mutations in tumor suppressor genes and proto-oncogenes: APC, TP53, SMAD2, SMAD4, DCC, KRAS, PIK3CA and loss of heterozygosity (LOH) in chromosomes 1, 5, 8, 17 and 18 are the most common causes of CIN.
Inactivation mutations of genes involved in DNA repair - MMR (mismatch repair) - MLH1, MSH2, MSH6, trigger the occurrence of multiple mutations and deletions. Epigenetic disorders are caused by genes promotor hypermethylation, known as CpG islands, and methylator phenotype silencing genes participating in DNA replication. The elucidation of genomic and epigenetic disorders and their role in colorectal cancerogenesis is essential for the development of effective prevention and therapy strategies for CRC patients.
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