Determination of dominat K-RAS mutation type and the effect of determined mutations on protein function and response in Aegean region rectosigmoid cancers

Tumors located at the rectum constitute 27% - 32 of the all colorectal group cancers. Tumors in this anatomic region have different processes in tumor and metastases behavior from other parts of the colon tumors. There is no exhaustive information in literature about K-RAS mutation of tumors located in rectum region. Objective: Purpose of this study was to determine K-RAS mutation status and identifying these mutations on protein function and tumor behavior of rectum located tumors. Method: Recto sigmoid cancer diagnosed patients between 2009-2011 years in Dokuz Eylul University Hospital enrolled to this study. DNA was isolated from paraffin embedded pathology blocks with spin column base DNA isolation method in Basic Oncology Department Laboratory. Isolated DNA was amplified with real time PCR to genetic analyses. Results: Recto sigmoid groups offered 11.4% G12D, 8.6% G12V and 5.7% of G12A mutations. %65.7 of cases with rectum tumors were wild type for KRAS mutations. For all that, colon groups offered 12.2% G12D, 10.2% G12V mutations. %69.4 of colon group was wild type for KRAS mutation. G12A and G12S mutations were not detected in colon groups like G12C and G13R mutations in rectum groups. The common mutation in the entire study group was G12D (%11, 9) mutation. Conclusion: Molecular and protein modeling studies demonstrate that KRAS mutant proteins have heterogeneous patterns of behavior. Clinical trials have continued about this behavior differences relations with treatment outcomes. Aggressive and slowly progressing K-RAS mutation phenotypes in recto sigmoid and colon study showed different distribution rates. There were no istaticsel relations between tumor behavior and treatment outcome in our study. This could be related to small number of study group. A well designed prospective study with large number of patients contributes to the literature. Key Words: rectosigmoid cancers, K-RAS genotype, K-RAS fenotype