1. Genomic predictors of interindividual differences in response to DNA damaging agents.
- Author
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Fry RC, Svensson JP, Valiathan C, Wang E, Hogan BJ, Bhattacharya S, Bugni JM, Whittaker CA, and Samson LD
- Subjects
- Alkylating Agents toxicity, Cell Line, Chromosomes, Human, Pair 21 genetics, DNA Glycosylases genetics, DNA Modification Methylases genetics, DNA Repair Enzymes genetics, Gene Expression drug effects, Gene Regulatory Networks drug effects, Genome, Human, Humans, Methylnitronitrosoguanidine toxicity, Open Reading Frames, Tumor Suppressor Proteins genetics, DNA Damage genetics, Mutagens toxicity
- Abstract
Human lymphoblastoid cells derived from different healthy individuals display considerable variation in their transcription profiles. Here we show that such variation in gene expression underlies interindividual susceptibility to DNA damaging agents. The results demonstrate the massive differences in sensitivity across a diverse cell line panel exposed to an alkylating agent. Computational models identified 48 genes with basal expression that predicts susceptibility with 94% accuracy. Modulating transcript levels for two member genes, MYH and C21ORF56, confirmed that their expression does indeed influence alkylation sensitivity. Many proteins encoded by these genes are interconnected in cellular networks related to human cancer and tumorigenesis.
- Published
- 2008
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