Analysis of the Thymidylate Synthase Gene Structure in Colorectal Cancer Patients and Its Possible Relation with the 5-Fluorouracil Drug Response

Thymidylate synthase (TS) catalyzes methylation of dUMP to dTMP and it is the target for the 5-Fluorouracil (5-FU) activity. Barbour et al. showed that variant structural forms of TS in tumour cell lines confer resistance to fluoropyrimidin...

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Main Authors: A. Calascibetta, Flavia Contino, S. Feo, G. Gulotta, M. Cajozzo, A. Antona, G. Sanguedolce, R. Sanguedolce
Format: Article
Language:English
Published: Wiley 2010-01-01
Series:Journal of Nucleic Acids
Online Access:http://dx.doi.org/10.4061/2010/306754
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author A. Calascibetta
Flavia Contino
S. Feo
G. Gulotta
M. Cajozzo
A. Antona
G. Sanguedolce
R. Sanguedolce
author_facet A. Calascibetta
Flavia Contino
S. Feo
G. Gulotta
M. Cajozzo
A. Antona
G. Sanguedolce
R. Sanguedolce
author_sort A. Calascibetta
collection DOAJ
description Thymidylate synthase (TS) catalyzes methylation of dUMP to dTMP and it is the target for the 5-Fluorouracil (5-FU) activity. Barbour et al. showed that variant structural forms of TS in tumour cell lines confer resistance to fluoropyrimidines. We planned to perform the whole TS gene structure by means of sequencing techniques in human colorectal cancer (CRC) samples to try to identify the presence of any possible TS variant form that could be responsible of fluoropyrimidines drug resistance and of the worse prognosis. We performed the TS-DNA gene sequence in 68 CRC from patients of A, B, and C Dukes' stages and different histological grade, but we did not find any mutation in the TS-DNA structure. In the future we intend to widen the TS structure analysis to the metastatic CRCs, because due to their higher genomic instability, they could present a TS variant form responsible of the fluoropyrimidines drug resistance and the worse prognosis.
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series Journal of Nucleic Acids
spelling doaj-art-2284fe57696243859265ca02b9fa81be2025-02-03T07:24:34ZengWileyJournal of Nucleic Acids2090-021X2010-01-01201010.4061/2010/306754306754Analysis of the Thymidylate Synthase Gene Structure in Colorectal Cancer Patients and Its Possible Relation with the 5-Fluorouracil Drug ResponseA. Calascibetta0Flavia Contino1S. Feo2G. Gulotta3M. Cajozzo4A. Antona5G. Sanguedolce6R. Sanguedolce7Dipartimento di Scienze Farmacologiche “Pietro Benigno,” Università degli Studi di Palermo, 90100 Palermo, ItalyDipartimento di Oncologia Sperimentale e Applicazioni Cliniche, Università degli Studi di Palermo, 90100 Palermo, ItalyDipartimento di Oncologia Sperimentale e Applicazioni Cliniche, Università degli Studi di Palermo, 90100 Palermo, ItalyChirurgia Generale e d'Urgenza, Università degli Studi di Palermo, 90100 Palermo, ItalyDipartimento di Discipline Chirurgiche ed Oncologiche, Università degli Studi di Palermo, 90100 Palermo, ItalyDipartimento di Scienze Farmacologiche “Pietro Benigno,” Università degli Studi di Palermo, 90100 Palermo, ItalyDipartimento di Scienze Farmacologiche “Pietro Benigno,” Università degli Studi di Palermo, 90100 Palermo, ItalyDipartimento di Scienze Farmacologiche “Pietro Benigno,” Università degli Studi di Palermo, 90100 Palermo, ItalyThymidylate synthase (TS) catalyzes methylation of dUMP to dTMP and it is the target for the 5-Fluorouracil (5-FU) activity. Barbour et al. showed that variant structural forms of TS in tumour cell lines confer resistance to fluoropyrimidines. We planned to perform the whole TS gene structure by means of sequencing techniques in human colorectal cancer (CRC) samples to try to identify the presence of any possible TS variant form that could be responsible of fluoropyrimidines drug resistance and of the worse prognosis. We performed the TS-DNA gene sequence in 68 CRC from patients of A, B, and C Dukes' stages and different histological grade, but we did not find any mutation in the TS-DNA structure. In the future we intend to widen the TS structure analysis to the metastatic CRCs, because due to their higher genomic instability, they could present a TS variant form responsible of the fluoropyrimidines drug resistance and the worse prognosis.http://dx.doi.org/10.4061/2010/306754
spellingShingle A. Calascibetta
Flavia Contino
S. Feo
G. Gulotta
M. Cajozzo
A. Antona
G. Sanguedolce
R. Sanguedolce
Analysis of the Thymidylate Synthase Gene Structure in Colorectal Cancer Patients and Its Possible Relation with the 5-Fluorouracil Drug Response
Journal of Nucleic Acids
title Analysis of the Thymidylate Synthase Gene Structure in Colorectal Cancer Patients and Its Possible Relation with the 5-Fluorouracil Drug Response
title_full Analysis of the Thymidylate Synthase Gene Structure in Colorectal Cancer Patients and Its Possible Relation with the 5-Fluorouracil Drug Response
title_fullStr Analysis of the Thymidylate Synthase Gene Structure in Colorectal Cancer Patients and Its Possible Relation with the 5-Fluorouracil Drug Response
title_full_unstemmed Analysis of the Thymidylate Synthase Gene Structure in Colorectal Cancer Patients and Its Possible Relation with the 5-Fluorouracil Drug Response
title_short Analysis of the Thymidylate Synthase Gene Structure in Colorectal Cancer Patients and Its Possible Relation with the 5-Fluorouracil Drug Response
title_sort analysis of the thymidylate synthase gene structure in colorectal cancer patients and its possible relation with the 5 fluorouracil drug response
url http://dx.doi.org/10.4061/2010/306754
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