Identification and functional analysis of single nucleotide polymorphism in the tandem repeat sequence of thymidylate synthase gene.

摘要: The variable number of tandem repeat (VNTR) thymidylate synthase (TS) gene, mainly 2 (2R) and 3 (3R), is one the genetic variations that can potentially predict effectiveness 5-fluorouracil-based chemotherapy. In this study we identified an additional single nucleotide polymorphism (SNP) in VNTR TS, followed by functional clinical analysis SNP. Two-hundred fifty eight tumor samples were obtained from patients with primary colorectal adenocarcinoma. We observed three different patterns electrophoresis 2R/3R heterozygote. sequencing results revealed a SNP, G/C polymorphism, within 28-bp component TS VNTR. Each polymorphic allele was assigned as 2G, 2C, 3G, or 3C according to combination SNP Functional showed plasmid construct 3G sequence had four times greater efficiency translation than other sequences. 3R cancer subdivided into around half indicating its commonness among Japanese. genotypes classified high expression type (2R/3G, 3C/3G, 3G/3G) low (2R/2R, 2R/3C, 3C/3C). who received oral fluoropyrimedines survived longer no treatment group type. No benefit These suggest double sequence, VNTR, may provide potential for more effective prediction outcome