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Genomic predictors of interindividual differences in response to DNA damaging agents.

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.

SUBMITTER: Fry RC 

PROVIDER: S-EPMC2559901 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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Genomic predictors of interindividual differences in response to DNA damaging agents.

Fry Rebecca C RC   Svensson J Peter JP   Valiathan Chandni C   Wang Emma E   Hogan Brad J BJ   Bhattacharya Sanchita S   Bugni James M JM   Whittaker Charles A CA   Samson Leona D LD  

Genes & development 20080919 19

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  ...[more]