Global gene expression in Ha-ras and B-raf mutated mouse liver tumors.

Chemically-induced mouse liver tumors harbor mutations in different oncogenes. About 50% of tumors contain activating mutations in the Ha-ras gene contain and about 20% of tumors show point mutations in the B-raf oncogene. We have investigated the gene expression profiles in tumors of the 2 genotypes by microarray analysis. In total, approximately 500 genes or expressed sequences were aberrantly expressed in tumors relative to normal liver tissue. Around two/thirds of them were significantly altered in both Ha-ras and B-raf mutated liver tumors, and most of the remaining genes showed at least qualitatively comparable changes in both tumor types. Several functional clusters were hypothesized in tumors of the 2 genotypes which involve alterations in a battery of genes encoding enzymes of lipid metabolism. The similarity in the patterns of global gene expression of Ha-ras and B-raf mutated liver tumors suggests that mutational activation of the 2 oncogenes results in activation of a common set of transcriptional regulators.