Involvement of microsatellite instability in colorectal cancer –review

BackgroundMicrosatellites, also known as Short Tandem Repeats (STRs) are short (1-6 base pairs) repeating segments of DNA scattered throughout the human genome, accounting for approximately 3% of it.Because of their repeated structure, microsatellites have a predisposition for high mutation rates.Microsatellite instability is a molecular phenotype determined by a defective DNA mismatch repair system (1-3).Microsatellite instability occurs in about 15% of gastrointestinal cancers, being associated with specific clinical, pathologic and molecular features of the tumors (4).The presence of microsatellite instability was found in the sporadic colon, gastric and endometrial cancers, but was also determined in many other cancers, such as ovarian cancer, sebaceous carcinoma, glioblastomas or lymphomas (5,6).Colorectal cancer has been defined as a genetically heterogenous disease, with two main different pathways being identified in the Review Open Access Abstract.Background.Microsatellites, also known as Short Tandem Repeats (STRs) are short (1-6 base pairs) repeating segments of DNA scattered throughout the human genome, accounting for approximately 3% of it.Microsatellite instability occurs in about 15% of gastrointestinal cancers, being associated with specific clinical, pathologic and molecular features of the tumors.Genetic mechanism, clinical features and treatment influence.Microsatellite instability (MSI) in colorectal cancers occurs through different mechanisms.MSI in sporadic colorectal cancer usually appears because of epigenetic silencing of the DNA mismatch repair gene MLH1, being associated with methylation.Regarding hereditary non-polyposis colorectal cancer (HNPPC ), all the cases present microsatellites that had changed in length, not only in the critical genetic region but virtually everywhere in the genome of the tumor.The common presence of microsatellite instability in HNPPC is related to the defective DNA mismatch repair proteins determined by germline mutation of one of the three main genes (MLH1, MSH2 and MSH6).In contrast to patients with chromosomal instability pathway (CIN), who present mutations in p53 and APC genes, including major chromosomal abnormalities, the patients who present MSI have mutations in specific genes, such as transforming growth factor beta receptor II (TGF-RII) and beta-catenin, with fewer mutations being found in p53 and K-ras genes.Also, there have been a number of studies regarding the response of patients diagnosed with colorectal cancer and microsatellite instability to various chemotherapy protocols.Conclusion.Understanding the genetic mechanisms of tumor development in patients with colorectal cancer involving the aspect of the microsatellite instability pathway has an important role in the diagnosis and prognosis of these patients, as well as a personalized surgical and chemotherapy treatment, with better oncological results.