ArticleCancer science2007
Genome-wide screening of loci associated with drug resistance to 5-fluorouracil-based drugs.
Article in Cancer science, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- The Human Tumor Atlas Network's beginning steps toward the future of collaborative multi-omic discovery.Cell reports. Medicine · 2022Article
- Polymorphisms of MTHFR and TYMS predict capecitabine-induced hand-foot syndrome in patients with metastatic breast cancer.Cancer communications (London, England) · 2019Article
- Detection of mutational patterns in cell-free DNA of colorectal cancer by custom amplicon sequencing.Molecular oncology · 2019Article
- Integration of Tumor Genomic Data with Cell Lines Using Multi-dimensional Network Modules Improves Cancer Pharmacogenomics.Cell systems · 2018Article
- Thymidylate synthase polymorphisms are associated to therapeutic outcome of advanced non-small cell lung cancer patients treated with platinum-based chemotherapy.Molecular biology reports · 2014Article
- Enhancement of 5-fluorouracil-induced cytotoxicity by leucovorin in 5-fluorouracil-resistant gastric cancer cells with upregulated expression of thymidylate synthase.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2014Article
- The transcription factor CREBZF is a novel positive regulator of p53.Cell cycle (Georgetown, Tex.) · 2012Article
- Thymidylate synthase protein expression by IHC and gene copy number by SISH correlate and show great variability in non-small cell lung cancer.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2012Article
- Gene expression signature analysis identifies vorinostat as a candidate therapy for gastric cancer.PloS one · 2011Article
- Amplification of thymidylate synthetase in metastatic colorectal cancer patients pretreated with 5-fluorouracil-based chemotherapy.European journal of cancer (Oxford, England : 1990) · 2010Article
- Significance of thymidylate synthase for resistance to pemetrexed in lung cancer.Cancer science · 2010Article
- Article
- Identification of genomic regions contributing to etoposide-induced cytotoxicity.Human genetics · 2009Article
- Effects of small interfering RNA targeting thymidylate synthase on survival of ACC3 cells from salivary adenoid cystic carcinoma.BMC cancer · 2008Article
- 5-Fluorouracil: mechanisms of resistance and reversal strategies.Molecules (Basel, Switzerland) · 2008Review
- Swainsonine reduces 5-fluorouracil tolerance in the multistage resistance of colorectal cancer cell lines.Molecular cancer · 2007Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Resistance to chemotherapeutic agents represents the chief cause of mortality in cancer patients with advanced disease. Chromosomal aberration and altered gene expression are the main genetic mechanisms of tumor chemoresistance. In this study, we have established an algorithm to calculate DNA copy number using the Affymetrix 10K array, and performed a genome-wide correlation analysis between DNA copy number and antitumor activity against 5-fluorouracil (5-FU)-based drugs (S-1, tegafur + uracil [UFT], 5'-DFUR and capecitabine) to screen for loci influencing drug resistance using 27 human cancer xenografts. A correlation analysis confirmed that the single nucleotide polymorphism (SNP) showing significant associations with drug sensitivity were concentrated in some cytogenetic regions (18p, 17p13.2, 17p12, 11q14.1, 11q11 and 11p11.12), and we identified some genes that have been indicated their relations to drug sensitivity. Among these regions, 18p11.32 at the location of the thymidylate synthase gene (TYMS) was strongly associated with resistance to 5-FU-based drugs. A change in copy number of the TYMS gene was reflected in the TYMS expression level, and showed a significant negative correlation with sensitivity against 5-FU-based drugs. These results suggest that amplification of the TYMS gene is associated with innate resistance, supporting the possibility that TYMS copy number might be a predictive marker of drug sensitivity to fluoropyrimidines. Further study is necessary to clarify the functional roles of other genes coded in significant cytogenetic regions. These promising data suggest that a comprehensive DNA copy number analysis might aid in the quest for optimal markers of drug response.
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Registered trials
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