Nucleic Acids Research Advance Access published online on March 1, 2007
Nucleic Acids Research, doi:10.1093/nar/gkm061
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Genomics |
Impaired expression of NER gene network in sporadic solid tumors
1Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-anexo, Porto Alegre 90035-003, Brazil, 2Instituto de Física, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves 9500, Porto Alegre 91501-970, Caixa Postal 15051, Brazil, 3Universidade Luterana do Brasil, Av. Itacolomi 3600, Gravataí 94170-240, Brazil and 4Centro de Ciências Rurais, Unipampa/São Gabriel - Pós-Graduação em Física, Prédio 13, Universidade Federal de Santa Maria, Santa Maria 97105-900, Brazil
*To whom correspondence should be addressed. Tel: +55 51 33085577; Fax: +55 51 33085540; Email: mauro{at}ufrgs.br Correspondence may also be addressed to Rita de Almeida. Tel: +55 51 33086521; Fax: +55 51 33086286; Email: rita{at}if.ufrgs.br
Received November 13, 2006. Revised December 28, 2006. Accepted January 19, 2007.
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.
The authors wish it to be known that, in their opinion, the first three authors should be regarded as joint First Authors
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