Impaired expression of NER gene network in sporadic solid tumors

• Published in: Nucleic acids research Vol. 35; no. 6; pp. 1859 - 1867
• Main Authors: Castro, Mauro A.A, Mombach, José C.M, de Almeida, Rita M.C, Moreira, José C.F
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.03.2007; Oxford Publishing Limited (England)
• Subjects: Apoptosis - genetics; Data Interpretation, Statistical; DNA Repair - genetics; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Genomics; Humans; Neoplasms - genetics; Point Mutation; Stochastic Processes
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gkm061

Nucleotide repair genes are not generally altered in sporadic solid tumors. However, point mutations are found scattered throughout the genome of cancer cells indicating that the repair pathways are dysfunctional. To address this point, in this work we focus on the expression pathways rather than in the DNA structure of repair genes related to either genome stability or essential metabolic functions. We present here a novel statistical analysis comparing ten gene expression pathways in human normal and cancer cells using serial analysis of gene expression (SAGE) data. We find that in cancer cells nucleotide-excision repair (NER) and apoptosis are the most impaired pathways and have a highly altered diversity of gene expression profile when compared to normal cells. We propose that genome point mutations in sporadic tumors can be explained by a structurally conserved NER with a functional disorder generated from its entanglement with the apoptosis gene network.