Delimiting Allelic Imbalance of TYMS by Allele-Specific Analysis.

作者: Emilia Balboa-Beltrán , Raquel Cruz , Angel Carracedo , Francisco Barros

DOI: 10.1097/MD.0000000000001091

关键词:

摘要: Allelic imbalance of thymidylate synthase (TYMS) is attributed to polymorphisms in the 5'- and 3'-untranslated region (UTR). These have been related risk suffering different cancers, for example leukemia, breast or gastric cancer, response drugs, among which are methotrexate glutamates, stavudine, specifically 5-fluorouracil (5-FU), as TYMS its direct target. A vast literature has published relation 5-FU, even suggesting sole use these effectively manage 5-FU dosage. Estimates extent influence expression past based on functional analysis by luciferase assays quantification mRNA, but both studies, association studies with cancer toxicity very contradictory. Regarding assays, artificial genetic environment created assay problems derived from quantitative polymerase chain reactions (qPCRs), a reference gene, may distorted results. To avoid sources interference, we analyzed allelic allelic-specific peripheral blood mononuclear cells (PBMCs) patients.Allelic PBMCs, taken 40 patients suspected myeloproliferative haematological diseases, was determined fluorescent fragment (for 3'-UTR polymorphism), Sanger sequencing qPCR multiplex 5'-UTR polymorphisms).For neither 3'- nor did observed exceed 1.5 fold. None statistically associated imbalance.The results acquired allow us deny previously established assertion an 2 4 fold rs45445694 rs2853542 narrow fold, our population. data circumscribe clinical outcome question their establishing dosage, above all when additional factors not considered.

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