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Polymorphic tandem repeats in the thymidylate synthase gene is associated with its protein expression in human gastrointestinal cancers.

AbstractBACKGROUND:
Thymidylate synthase (TS) is a target enzyme of 5-fluorouracil (5-FU), and the TS gene has a polymorphic tandem repeated sequence in the 5'-untranslated region. We investigated the polymorphism on the repeat length of the TS gene and its relation to the number of 5-fluoro-dUMP (FdUMP) binding sites in human gastrointestinal cancers.
MATERIALS AND METHODS:
Seventy adenocarcinoma samples were used. Twenty-one patients received UFT and 49 patients received no treatment before surgery. Tandem repeat length of TS gene was determined by PCR amplification of genomic DNA. The number of FdUMP binding sites were measured by 3H-FdUMP binding assay.
RESULTS:
Double- (2R) and triple-repeated (3R) sequences of the TS gene were found in the cancer tissues. Three genotypes of TS were found: 2R/2R (n = 3), 2R/3R (n = 16) and 3R/3R (n = 51). The free TS level for the 3R/3R genotype was significantly higher than for the 2R/3R genotype in UFT (+) group. Similar genotype-dependent difference of TS level was observed in UFT (-) group.
CONCLUSIONS:
Our results suggest the link between TS genotype and TS protein expression. This link might offer an advantage for selection of patients to receive 5-FU-based chemotherapy.
AuthorsK Kawakami, K Omura, E Kanehira, Y Watanabe
JournalAnticancer research (Anticancer Res) 1999 Jul-Aug Vol. 19 Issue 4B Pg. 3249-52 ISSN: 0250-7005 [Print] Greece
PMID10652619 (Publication Type: Journal Article)
Chemical References
  • 5' Untranslated Regions
  • DNA, Neoplasm
  • Fluorodeoxyuridylate
  • Thymidylate Synthase
Topics
  • 5' Untranslated Regions
  • Base Sequence
  • Binding Sites
  • DNA, Neoplasm
  • Fluorodeoxyuridylate (metabolism)
  • Gastrointestinal Neoplasms (enzymology, genetics)
  • Genotype
  • Humans
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Tandem Repeat Sequences
  • Thymidylate Synthase (genetics)

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