1. Expression quantitative trait analysis reveals fine germline transcript regulation in mouse lung tumors.
- Author
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Cotroneo, Chiara E., Dassano, Alice, Colombo, Francesca, Pettinicchio, Angela, Lecis, Daniele, Dugo, Matteo, De Cecco, Loris, Dragani, Tommaso A., and Manenti, Giacomo
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GENE expression , *LUNG tumors , *GERM cells , *CANCER genetics , *GENETIC transcription regulation , *LABORATORY mice , *ALLELES , *ANIMAL experimentation , *DISEASE susceptibility , *GENES , *GENETIC polymorphisms , *GENETICS , *MICE , *PHOSPHOTRANSFERASES , *PROTEINS , *PHENOTYPES , *GENE expression profiling , *GENOTYPES - Abstract
Gene expression modulates cellular functions in both physiologic and pathologic conditions. Herein, we carried out a genetic linkage study on the transcriptome of lung tumors induced by urethane in an (A/J x C57BL/6)F4 intercross population, whose individual lung tumor multiplicity (Nlung) is linked to the genotype at the Pulmonary adenoma susceptibility 1 (Pas1) locus. We found that expression levels of 1179 and 1579 genes are modulated by an expression quantitative trait locus (eQTL) in cis and in trans, respectively (LOD score > 5). Of note, the genomic area surrounding and including the Pas1 locus regulated 14 genes in cis and 857 genes in trans. In lung tumors of the same (A/J x C57BL/6)F4 mice, we found 1124 genes whose transcript levels associated with Nlung (FDR < 0.001). The expression levels of about a third of these genes (n = 401) were regulated by the genotype at the Pas1 locus. Pathway analysis of the sets of genes associated with Nlung and regulated by Pas1 revealed a set of 14 recurrently represented genes that are components or targets of the Ras-Erk and Pi3k-Akt signaling pathways. Altogether our results illustrate the architecture of germline control of gene expression in mouse lung cancer: they highlight the importance of Pas1 as a tumor-modifier locus, attribute to it a novel role as a major regulator of transcription in lung tumor nodules and strengthen the candidacy of the Kras gene as the effector of this locus. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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