Calascibetta A, Contino Flavia, Feo S, Gulotta G, Cajozzo M, Antona A, Sanguedolce G, Sanguedolce R
Dipartimento di Scienze Farmacologiche "Pietro Benigno," Università degli Studi di Palermo, 90100 Palermo, Italy.
J Nucleic Acids. 2010 Jan 26;2010:306754. doi: 10.4061/2010/306754.
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.
胸苷酸合成酶（TS）催化脱氧尿苷一磷酸（dUMP）甲基化生成脱氧胸苷一磷酸（dTMP），它是5-氟尿嘧啶（5-FU）发挥作用的靶点。巴伯等人表明，肿瘤细胞系中TS的变异结构形式赋予了对氟嘧啶的抗性。我们计划通过测序技术对人类结直肠癌（CRC）样本进行完整的TS基因结构分析，以试图确定是否存在任何可能导致氟嘧啶耐药性及预后较差的TS变异形式。我们对处于A、B和C期杜克分期以及不同组织学分级的68例CRC患者进行了TS-DNA基因测序，但未在TS-DNA结构中发现任何突变。未来我们打算将TS结构分析扩展至转移性CRC，因为由于其较高的基因组不稳定性，它们可能存在一种导致氟嘧啶耐药性及预后较差的TS变异形式。
