Tumoral expression of TS may be a prognostic marker in colorectal cancer patients and may predict the sensitivity to 5-Fluorouracil-based chemotherapy. The TS gene promoter enhancer region contains two different polymorphisms, which can influence the TS mRNA transcriptional efficiency. The first is a polymorphism of the tandem repeat sequence (2 or 3 repeats), the second is a single nucleotide polymorphism (SNP) (G>C) in the second repeat of the 3R alleles that can abolish the increased transcriptional activity of 3R alleles relative to the 2R. We studied the tumoral TS mRNA expression levels and compared this parameter with the colonic mucosa TS gene polymorphisms in 48 colorectal cancer patients undergoing surgery and receiving post-operative 5-Fluorouracil-based chemotherapy. TS mRNA levels were determined by quantitative real time reverse transcriptase-polymerase chain reaction (PCR) and TS gene polymorphism by PCR followed by electrophoresis (2R/3R polymorphism) and HaeIII restriction digestion (G>C). Median TS/G6PDH expression ratio was 1.52 (range 0–10.72). TS genotype frequencies were 18.7% (2R/2R), 47.9% (2R/3R) and 33.3% (3R/3R). A trend for increased TS gene expression in patients with the 3R/3R genotype vs patients with the 2R/2R or the 2R/3R genotypes was observed (median TS/G6PDH ratio 2.2 and 1.4 for 3R/3R and 2R/2R-2R/3R groups, respectively) (p=0.07). On the basis of the SNP investigation, we stratified TS genotype into 3 sub-groups: 2R/2R, 2R/3RC, 2R/3RG sub-group 1 (n=31) vs 3RG/3RG sub-group 2 (n=6) or vs 3RG/3RC sub- group 3 (n=7). We observed a statistically significant difference in the comparison of sub-group 1 with sub-group 2 only (p=0.004). Despite the limited number of patients, our results suggest that in 3R/3R patients SNP represents the most important factor in determining TS mRNA expression levels. In conclusion the addition of SNP to the TS gene tandem repeat sequence polymorphism may provide more effective prediction of sensitivity to 5-FU-based chemotherapy.
Morganti, M., Ciantelli, M., Giglioni, B., Putignano, A. L., Nobili, S., Papi, L., Landini, I., Napoli, C., Valanzano, R., Cianchi, F., Boddi, V., Tonelli, F., Cortesini, C., Mazzei, T., Genuardi, M., Mini, E., CORRELATION BETWEEN THYMIDYLATE SYNTHASE (TS) mRNA EXPRESSION AND TS GENE PROMOTER POLYMORPHISMS IN PRIMARY COLORECTAL CANCER PATIENTS, <<ANNALS OF ONCOLOGY>>, 2004; 64 (7): 866-867 [https://hdl.handle.net/10807/219882]
CORRELATION BETWEEN THYMIDYLATE SYNTHASE (TS) mRNA EXPRESSION AND TS GENE PROMOTER POLYMORPHISMS IN PRIMARY COLORECTAL CANCER PATIENTS
Genuardi, Maurizio;
2004
Abstract
Tumoral expression of TS may be a prognostic marker in colorectal cancer patients and may predict the sensitivity to 5-Fluorouracil-based chemotherapy. The TS gene promoter enhancer region contains two different polymorphisms, which can influence the TS mRNA transcriptional efficiency. The first is a polymorphism of the tandem repeat sequence (2 or 3 repeats), the second is a single nucleotide polymorphism (SNP) (G>C) in the second repeat of the 3R alleles that can abolish the increased transcriptional activity of 3R alleles relative to the 2R. We studied the tumoral TS mRNA expression levels and compared this parameter with the colonic mucosa TS gene polymorphisms in 48 colorectal cancer patients undergoing surgery and receiving post-operative 5-Fluorouracil-based chemotherapy. TS mRNA levels were determined by quantitative real time reverse transcriptase-polymerase chain reaction (PCR) and TS gene polymorphism by PCR followed by electrophoresis (2R/3R polymorphism) and HaeIII restriction digestion (G>C). Median TS/G6PDH expression ratio was 1.52 (range 0–10.72). TS genotype frequencies were 18.7% (2R/2R), 47.9% (2R/3R) and 33.3% (3R/3R). A trend for increased TS gene expression in patients with the 3R/3R genotype vs patients with the 2R/2R or the 2R/3R genotypes was observed (median TS/G6PDH ratio 2.2 and 1.4 for 3R/3R and 2R/2R-2R/3R groups, respectively) (p=0.07). On the basis of the SNP investigation, we stratified TS genotype into 3 sub-groups: 2R/2R, 2R/3RC, 2R/3RG sub-group 1 (n=31) vs 3RG/3RG sub-group 2 (n=6) or vs 3RG/3RC sub- group 3 (n=7). We observed a statistically significant difference in the comparison of sub-group 1 with sub-group 2 only (p=0.004). Despite the limited number of patients, our results suggest that in 3R/3R patients SNP represents the most important factor in determining TS mRNA expression levels. In conclusion the addition of SNP to the TS gene tandem repeat sequence polymorphism may provide more effective prediction of sensitivity to 5-FU-based chemotherapy.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.