Microsatellite instability (MSI and EMAST) in molecular profiling of sporadic colon cancer (MSIandEMASTinCRC)
Sanja Kapitanović, dr.sc.
+385 1 456 1108
Cancer is one of the most important health issues of today and number of cancer cases is expected to increase in the future. Colon cancer is one of the most common cancers and the second leading cause of cancer death in the Western world.
Most cases of colon cancer occur in sporadic form and follow the adenoma-carcinoma sequence. The development of the sporadic colon cancer is a result of the accumulation of sporadic mutations in many different genes, oncogenes, tumor suppressor genes as well as mismatch repair genes. It is known that microsatellite instability (MSI) as well as microRNAs (miRNAs) as regulators of gene expression also have a role in sporadic colon cancer tumorigenesis. Elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) is a form of microsatellite instability that is initiated by inflammation and modulates colon cancer progression.
The results of our previous study suggest the role of inflammatory cytokines in colon cancer tumorigenesis. In this project the research will be extended to NLRP3 inflammasoma, a potent inducer of proinflammatory cytokines.
The main goal of this project is to investigate MSI and EMAST microsatellite instability in sporadic colon cancer and to correlate the obtained results with clinico-pathological characteristics of tumors and patients. Tumors will be molecularly profiled with regard to frequency and distribution of MSI and EMAST and mutations in key cancer pathways (KRAS/BRAF, PIK3CA, p53). In addition results will be correlated with patients’ inherited genetic profiles based on inflammasome NLRP3 and cytokine polymorphisms as well as expression of specific genes on mRNA, miRNA and protein level.
We expect that our results will contribute to the elucidation of molecular basis of sporadic colon cancer, and be useful in patients’ surveillance and treatment.