Non-homologous end-joining genes are not inactivated in human radiation-induced sarcomas with genomic instability.
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.
Institut Curie - CNRS - UPMC UMR7147, CEA LRC38, Paris, France.
Sandrine H
SH
Lefèvre
Arnaud
A
Coquelle
Nathalie
N
Gonin-Laurent
Andrej
A
Cör
Nicolas
N
Vogt
Laurent
L
Chauveinc
Philippe
P
Anract
Bernard
B
Dutrillaux
Sylvie
S
Chevillard
Bernard
B
Malfoy
D004249:DNA Damage / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics* / Q000528:radiation effects*; D020868:Gene Silencing / Q000528:radiation effects*; D014644:Genetic Variation / Q000235:genetics; D042822:Genomic Instability / Q000235:genetics* / Q000528:radiation effects*; D006801:Humans; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D012509:Sarcoma / Q000235:genetics*; D014407:Tumor Cells, Cultured