On the absence of mutations in nucleotide excision repair genes in sporadic solid tumors

• Published in: Genetics and molecular research 2008-01, Vol.7 (1), p.152-160
• Main Authors: Mombach, J C M, Castro, M A A, Moreira, J C F, de Almeida, R M C
• Format: Article
• Language: English
• Subjects: Apoptosis - genetics; DNA Repair - genetics; Gene Regulatory Networks; Genomic Instability; Humans; Neoplasms - genetics; Point Mutation
• ISSN: 1676-5680; 1676-5680
• DOI: 10.4238/vol7-1gmr393

In general, stochastic tumors show genomic instability associated with the proliferation of DNA point mutations, that is, a mutator phenotype. This feature cannot be explained by a dysfunctional mismatch repair alone, and indicates that nucleotide excision repair (NER) and/or base excision repair should be suppressed. However, mutations in NER genes are not causally implicated in the oncogenesis of sporadic solid tumors, according to the Cancer Gene Census at http://www.sanger.ac.uk/genetics/CGP/Census/. This brings up an apparent paradox: how to explain the recurrent non-existence in NER genes of somatic mutations causally related to cancer? In a recent study, we have shown that the origin of point mutations in cancer cell genomes can be explained by a structurally conserved NER with a functional disorder generated from its entanglement with a disabled apoptosis gene network. In the present study, we further characterize NER gene network properties and show that it has a highly connected architecture. This feature suggests that the absence of mutations in NER genes in sporadic solid tumors is a result of their participation in many essential cellular functions.