ArticlePharmacogenetics and genomics2011
Gene set analysis of purine and pyrimidine antimetabolites cancer therapies.
Article in Pharmacogenetics and genomics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Purinergic signal transduction and metabolic regulation by ENTPD5 and ENTPD6.Frontiers in endocrinology · 2026Review
- Ectonucleoside triphosphate diphosphohydrolase 6: A double-edged sword in cancer prognosis and therapy.World journal of clinical oncology · 2025Article
- Fusobacterium nucleatum-triggered purine metabolic reprogramming drives tumorigenesis in head and neck carcinoma.Discover oncology · 2023Article
- Dominant neoantigen verification in hepatocellular carcinoma by a single-plasmid system coexpressing patient HLA and antigen.Journal for immunotherapy of cancer · 2023Article
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- Calcium-activated nucleotides 1 (CANT1)-driven nuclear factor-k-gene binding (NF-ĸB) signaling pathway facilitates the lung cancer progression.Bioengineered · 2022Article
- CANT1 serves as a potential prognostic factor for lung adenocarcinoma and promotes cell proliferation and invasion in vitro.BMC cancer · 2022Article
- Determination of Breast Metabolic Phenotypes and Their Associations With Immunotherapy and Drug-Targeted Therapy: Analysis of Single-Cell and Bulk Sequences.Frontiers in cell and developmental biology · 2022Article
- Nucleotide de novo synthesis increases breast cancer stemness and metastasis via cGMP-PKG-MAPK signaling pathway.PLoS biology · 2020Article
- Clinicopathological features and prognostic value of SOX11 in childhood acute lymphoblastic leukemia.Scientific reports · 2020Article
- Article
- Potential Mechanisms Connecting Purine Metabolism and Cancer Therapy.Frontiers in immunology · 2018Review
- Computational discovery of transcription factors associated with drug response.The pharmacogenomics journal · 2016Article
- Reconstruction of Tissue-Specific Metabolic Networks Using CORDA.PLoS computational biology · 2016Article
- Population-based in vitro hazard and concentration-response assessment of chemicals: the 1000 genomes high-throughput screening study.Environmental health perspectives · 2015Article
- Molecular insight into thiopurine resistance: transcriptomic signature in lymphoblastoid cell lines.Genome medicine · 2015Article
- In vitro human cell line models to predict clinical response to anticancer drugs.Pharmacogenomics · 2015Review
- Integrative gene set analysis: application to platinum pharmacogenomics.Omics : a journal of integrative biology · 2014Article
- Pathway analysis of genome-wide data improves warfarin dose prediction.BMC genomics · 2013Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveResponses to therapies, either with regard to toxicities or efficacy, are expected to involve complex relationships of gene products within the same molecular pathway or functional gene set. Therefore, pathways or gene sets, as opposed to single genes, may better reflect the true underlying biology and may be more appropriate units for analysis of pharmacogenomic studies. Application of such methods to pharmacogenomic studies may enable the detection of more subtle effects of multiple genes in the same pathway that may be missed by assessing each gene individually.
methodsA gene set analysis of 3821 gene sets is presented assessing the association between basal messenger RNA expression and drug cytotoxicity using ethnically defined human lymphoblastoid cell lines for two classes of drugs: pyrimidines [gemcitabine (dFdC) and arabinoside] and purines [6-thioguanine and 6-mercaptopurine].
resultsThe gene set nucleoside-diphosphatase activity was found to be significantly associated with both dFdC and arabinoside, whereas gene set γ-aminobutyric acid catabolic process was associated with dFdC and 6-thioguanine. These gene sets were significantly associated with the phenotype even after adjusting for multiple testing. In addition, five associated gene sets were found in common between the pyrimidines and two gene sets for the purines (3',5'-cyclic-AMP phosphodiesterase activity and γ-aminobutyric acid catabolic process) with a P value of less than 0.0001. Functional validation was attempted with four genes each in gene sets for thiopurine and pyrimidine antimetabolites. All four genes selected from the pyrimidine gene sets (PSME3, CANT1, ENTPD6, ADRM1) were validated, but only one (PDE4D) was validated for the thiopurine gene sets.
conclusionIn summary, results from the gene set analysis of pyrimidine and purine therapies, used often in the treatment of various cancers, provide novel insight into the relationship between genomic variation and drug response.
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