Goldberg Z I, Cummings B J, Chapman W B, Klamut H J, Rauth A M
Department of Radiation Oncology, Ontario Cancer Institute/Princess Margaret Hospital, Toronto, Canada.
Int J Radiat Oncol Biol Phys. 1998 Sep 1;42(2):331-4. doi: 10.1016/s0360-3016(98)00234-x.
To determine, retrospectively, the status of the bp 609 mutation in the DT-diaphorase gene in anal canal carcinoma patients who have undergone radical radiotherapy with concurrent 5-fluorouracil (5-FU) and mitomycin C (MMC), to determine the relationship of the mutant form of the gene to treatment outcomes.
Paraffin blocks of pretreatment tumor biopsies were obtained on 49 patients who underwent treatment with curative intent using radiation, infusional 5-FU and bolus MMC from January 1991 to December 1993. DNA was extracted and subjected to polymerase chain reaction (PCR) analysis using primers that encompassed the bp 609 C to T mutation. Restriction endonuclease cleavage with Hinf 1 and gel electrophoresis were used to determine the polymorphism status of each patient.
DNA of 46 patients was successfully amplified. The 46 patients were distributed as follows: 26 (56.5%) C/C-homozygous wildtype, 18 (39%) T/C-heterozygous, and 2 (4.5%) T/T-homozygous mutant. Eleven of 46 patients had suffered treatment failure. The status of the bp 609 polymorphism in this group was 5 (45.5%) C/C, 5 (45.5%) C/T, and 1 (9%) T/T.
In this series, there was not an overrepresentation of the mutant allele in patients with treatment failure, suggesting that the bp 609 alteration is not a strong determinant of treatment outcome.
回顾性确定接受根治性放疗并同步使用5-氟尿嘧啶（5-FU）和丝裂霉素C（MMC）的肛管癌患者中DT-二氢嘧啶脱氢酶基因bp 609突变的情况，以确定该基因突变形式与治疗结果的关系。
获取了1991年1月至1993年12月期间49例接受根治性放疗、持续输注5-FU和推注MMC治疗的患者的治疗前肿瘤活检石蜡块。提取DNA，并使用涵盖bp 609 C至T突变的引物进行聚合酶链反应（PCR）分析。用Hinf 1进行限制性内切酶切割并通过凝胶电泳确定每位患者的多态性状态。
46例患者的DNA成功扩增。46例患者的分布如下：26例（56.5%）为C/C纯合野生型，18例（39%）为T/C杂合型，2例（4.5%）为T/T纯合突变型。46例患者中有ll例治疗失败。该组中bp 609多态性状态为5例（45.5%）C/C、5例（45.5%）C/T和1例（9%）T/T。
在本系列研究中，治疗失败患者中突变等位基因并无过度表现，这表明bp 609改变并非治疗结果的强决定因素。
