Molecular analysis of the polymorphisms of thymidylate synthase on cell-free circulating DNA in blood of patients with advanced colorectal carcinoma.
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Molecular analysis of the polymorphisms of thymidylate synthase on cell-free circulating DNA in blood of patients with advanced colorectal carcinoma. / Schwarzenbach, Heidi; Goekkurt, Eray; Pantel, Klaus; Aust, Danila E; Stoehlmacher, Jan.
In: INT J CANCER, Vol. 127, No. 4, 4, 2010, p. 881-888.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Molecular analysis of the polymorphisms of thymidylate synthase on cell-free circulating DNA in blood of patients with advanced colorectal carcinoma.
AU - Schwarzenbach, Heidi
AU - Goekkurt, Eray
AU - Pantel, Klaus
AU - Aust, Danila E
AU - Stoehlmacher, Jan
PY - 2010
Y1 - 2010
N2 - As a key enzyme in folate metabolism, the thymidylate synthase (TS) is important for the synthesis of nucleotides. Its polymorphisms may affect the TS gene expression and the susceptibility for Fluoropyrimidine (FU)-based chemotherapies. In this study, we assessed the relationship between the TS genotypes and clinical outcome to 5-FU-based chemotherapy, and examined whether cell-free circulating DNA is applicable for these molecular analyses. We combined the variable number tandem repeat (VNTR) and single nucleotide (SNP) polymorphisms of the TS promoter and the deletion variants (1494del6) in the 3UTR with the occurrence of loss of heterozygosity (LOH) at the microsatellite markers D18S59, D18S1140 and D18S976 mapped up- and downstream to the TS locus. Cell-free blood DNA, tumor tissues and leukocytes of 51 patients with advanced colorectal cancer were used. Genotyping revealed linkage disequilibrium between TS promoter and 3UTR (p=0.03) in blood and leukocytes. Inverse associations of the response to therapy with the number of polymorphisms (p=0.05) and the 494del6 polymorphism (p
AB - As a key enzyme in folate metabolism, the thymidylate synthase (TS) is important for the synthesis of nucleotides. Its polymorphisms may affect the TS gene expression and the susceptibility for Fluoropyrimidine (FU)-based chemotherapies. In this study, we assessed the relationship between the TS genotypes and clinical outcome to 5-FU-based chemotherapy, and examined whether cell-free circulating DNA is applicable for these molecular analyses. We combined the variable number tandem repeat (VNTR) and single nucleotide (SNP) polymorphisms of the TS promoter and the deletion variants (1494del6) in the 3UTR with the occurrence of loss of heterozygosity (LOH) at the microsatellite markers D18S59, D18S1140 and D18S976 mapped up- and downstream to the TS locus. Cell-free blood DNA, tumor tissues and leukocytes of 51 patients with advanced colorectal cancer were used. Genotyping revealed linkage disequilibrium between TS promoter and 3UTR (p=0.03) in blood and leukocytes. Inverse associations of the response to therapy with the number of polymorphisms (p=0.05) and the 494del6 polymorphism (p
M3 - SCORING: Zeitschriftenaufsatz
VL - 127
SP - 881
EP - 888
JO - INT J CANCER
JF - INT J CANCER
SN - 0020-7136
IS - 4
M1 - 4
ER -
