Mutation types analysis of selected biological markers for colorectal carcinom and their influence on the distant metastasis development rate

[D. S. Jugović]

156 str.

Biografija i bibliografija autora: str. 149-153. Библиографија: стр. 126-146.

Cell biology. Molecular genetics

Colorectal carcinoma (CRC) is a multifactorial disease caused by several genetic and epigenetic changes responsible for the disruption of the homeostasis of the cell. Therefore, there are a number of biological markers that can be used for monitoring, therapy, and disease outcomes in CRC patients. The development of genetics and molecular diagnostics led to significant progress in the definition of prognostic and predictive biomarkers of CRC which led to the increase in five-year survival, which is still not satisfactory. This doctoral dissertation aimed to find and define biological markers of CRC patients from Southern and Eastern Serbia capable to indicate a more aggressive behavior of tumors and to enable a more precise assessment of the course and outcome of the disease as well as the response to the application of standard chemotherapy. The mutational status of the KRAS, NRAS и EGFR gene was analyzed using reverse hybridization and real-time PCR. Relative telomere length was evaluated using real-time PCR. The activity of hTERT was done immunohistochemically. The results of this research showed a significant association between the development of distant metastases in the liver and the right-sided location of the primary tumor with the faster development of distant metastases. A more aggressive tumor behavior was indicated by the presence of the highest degree of tumor budding, longer telomere length and the presence of mutations in the KRAS gene. Compared to other mutations in KRAS, the presence of mutated G12A indicated biologically less aggressive CRC and a better response to standard chemotherapy. Right-sided tumor localization, higher T and N stage of the primary tumor at the time of diagnosis and shorter time to the development of distant metastases were singled out as independent predictors of shorter survival

colorectal cancer, distant metastases, tumor budding, telomerase, relative telomere length, KRAS, NRAS, EGFR

колоректални карцином, удаљене метастазе, туморско пупљење, теломераза, релативна дужина теломера, KRAS, NRAS, EGFR

577.2:616-00.6(043.3)

B 007; B 200; B 220; B 726; B 790

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