Impact of microsatellite status ( MSI ) with KRAS/NRAS and BRAF mutations for a colorectal cancer, a case report

Hereditary Non polyposis colorectal cancer (HNPCC) or Lynch syndrome is due to germ line mutation of one the DNA Mismatch Repair genes (MMR). In tumor cells, immunohistochemistry detects the loss of expression of either MLH1, MSH2, MSH6 or PMS2 protein, corresponding to the mutated genes. These mutations are associated with an unstable phenotype in tumor DNA characterized by new microsatellite alleles that are absent in matching normal DNA. Genetic studies have demonstrated that mutations of the KRAS/NRAS and BRAF in the MAPK pathway, are detected in a high proportion of CRC patients, including those with defective MMR activity. Elucidation of the microsatellite status of HNPCC patients may indicate what type of adjuvant chemotherapy is the most beneficial for a particular patient. Therefore, knowledge of MMR activity and KRAS/BRAF mutation status may provide further valu able guidance for planning therapeutic strategies. A series of investigations led to the realization that MSI arises from defects in the DNA mismatch repair (MMR) system and the identification of the 4 genes that cause Lynch syndrome. Particularly HNPCC patients with MSS and mutated KRAS or BRAF, who have poorer overall survival rates than patients with microsatellite instability. Knowledge of the microsatel lite status of patients and whether they harbor KRAS or BRAF mutations may enable more effective therapeutic strategies to be developed. In the present study, the microsatellite status and genetic mutations of KRAS/NRAS and BRAF (V600E) were characterized in CRC tissue in a patient (age, 53; male, in Iran ) as the clinical and pathologically diagnostic criteria for HNPCC.

کلیدواژه ها:

Hereditary Non polyposis colorectal cancer ، KRAS ، BRAF ، MMR ، MSI ، CRC