Non-homologous end-joining genes are not inactivated in human radiation-induced sarcomas with genomic instability
| Autor: | Nathalie Gonin-Laurent, Nicolas Vogt, Bernard Dutrillaux, Philippe Anract, Andrej Cör, Sylvie Chevillard, Laurent Chauveinc, Sandrine Lefevre, Arnaud Coquelle, Bernard Malfoy |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Genome instability
Ku80 Neoplasms Radiation-Induced Health Toxicology and Mutagenesis DNA Mutational Analysis Biology medicine.disease_cause Genomic Instability Loss of heterozygosity medicine Tumor Cells Cultured Humans Radiology Nuclear Medicine and imaging Gene Silencing Genetics Mutation Ku70 Radiation Genetic Variation Sarcoma DNA repair protein XRCC4 Non-homologous end joining Gene Expression Regulation Neoplastic enzymes and coenzymes (carbohydrates) Rad50 DNA Damage |
| Zdroj: | Journal of radiation research. 46(2) |
| ISSN: | 0449-3060 |
| Popis: | DNA double-strand break (DSB) repair pathways are implicated in the maintenance of genomic stability. However the alterations of these pathways, as may occur in human tumor cells with strong genomic instability, remain poorly characterized. We analyzed the loss of heterozygosity (LOH) and the presence of mutations for a series of genes implicated in DSB repair by non-homologous end-joining in five radiation-induced sarcomas devoid of both active Tp53 and Rb1. LOH was recurrently observed for 8 of the 9 studied genes (KU70, KU80, XRCC4, LIG4, Artemis, MRE11, RAD50, NBS1) but not for DNA-PKcs. No mutation was found in the remaining allele of the genes with LOH and the mRNA expression did not correlate with the allelic status. Our findings suggest that non-homologous end-joining repair pathway alteration is unlikely to be involved in the high genomic instability observed in these tumors. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|