Association of KRAS Gene and microRNA-124-3p in Sporadic Colorectal Tumours

Aim: To reveal the exonic and 3’UTR sequences of KRAS, TP53, APC, BRAF, PIK3CA genes in sporadic colorectal tumors and to investigate the clinical relevance of 3’UTR variations in miRNA profiles. Methods: In the study, the exonic and 3’UTR sequences of five genes in 12 sporadic colorectal tumors were extracted by next generation sequencing. In tumors with variation in the 3’UTR region, the changes caused by the variation in the miRNA binding profile were detected. The expression profile of these miRNAs in colorectal and other solid tumors compared to normal tissue was determined. Pathway analysis was performed to determine which signaling pathways miRNAs affect. Results: Case-10 in our study was wild type KRAS and received cetuximab treatment and developed drug resistance. In this case, it was concluded that the expression of KRAS increased and tumorigenesis progressed due to miRNAs that do not bind to this region due to variations in the 3’UTR region. Among these miRNAs, hsa-miR-124-3p was found to have decreased expression in colorectal tumors and to be associated with the ECM-receptor interaction pathway. Conclusion: Variations in the 3’UTR regions of genes critical in the process of carsinogenesis are associated with drug resistance and the process of tumorigenesis.

Studies on abacavir-induced hypersensitivity reaction:a successful example of translation of pharmacogenetics to personalized medicine

Abacavir is an effective nucleoside analog reverse transcriptase inhibitor used to treat human immunodeficiency virus(HIV) infected patients.Its main side effect is hypersensitivity reaction(HSR).The incidence of the HSR is associated with ethnicity among patients exposed to abacavir,and retrospective and prospective studies show a significantly increased risk of abacavir-induced HSR in human leukocyte antigen(HLA)-B*57:01-carrying patients.Immunological studies indicated that abacavir interacts specifically with HLA-B*57:01 and changed the binding specificity between the HLA molecule and the HLA-presented endogenous peptide repertoire,leading to a systemic autoimmune reaction.HLA-B*57:01 screening,combined with patch testing,had clinically predictive value and cost-effective impact in reducing the incidence of abacavir-induced HSR regardless of the HLA-B*57:01 prevalence in the population.Therefore,the US Food and Drug Administration(FDA) and international HIV treatment guidelines recommend a routine HLA-B*57:01 screening prior to abacavir treatment to decrease false positive diagnosis and prevent abacavir-induced HSR.The studies of abacavir-induced HSR and the implementation of the HLA-B*57:01 screening in the clinic represent a successful example of the use of pharmacogenetics for personalized diagnosis and therapy.