Author/Editor		Lefevre, Sandrine H; Coquelle, Arnaud; Gonin-Laurent, Nathalie; Coer, Andrej; Vogt, Nicolas; Chauveinc, Laurent; Anract, Philippe; Dutrillaux, Bernard; Chevillard, Sylvie; Malfoy, Bernard
Title		Non-homologous end-joining genes are not inactivated in human radiation-induced sarcomas with genomic instability
Type		članek
Source		J Radiat Res (Tokyo)
Vol. and No.		Letnik 46, št. 2
Publication year		2005
Volume		str. 223-31
Language		eng
Abstract		Radiation-induced tumor/Sarcoma/Non-homologous end-joining/Genomic instability/Mutations. 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 Rb 1. 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.
Descriptors		NEOPLASMS, RADIATION-INDUCED SARCOMA GENE EXPRESSION REGULATION, NEOPLASTIC DNA DAMAGE TUMOR CELLS, CULTURED VARIATION (GENETICS) DNA MUTATIONAL ANALYSIS