Human rRNA gene clusters are recombinational hotspots in cancer

Cancer Research
Dawn M StultsAndrew J Pierce

Abstract

The gene that produces the precursor RNA transcript to the three largest structural rRNA molecules (rDNA) is present in multiple copies and organized into gene clusters. The 10 human rDNA clusters represent <0.5% of the diploid human genome but are critically important for cellular viability. Individual genes within rDNA clusters possess very high levels of sequence identity with respect to each other and are present in high local concentration, making them ideal substrates for genomic rearrangement driven by dysregulated homologous recombination. We recently developed a sensitive physical assay capable of detecting recombination-mediated genomic restructuring in the rDNA by monitoring changes in lengths of the individual clusters. To prove that this dysregulated recombination is a potential driving force of genomic instability in human cancer, we assayed the rDNA for structural rearrangements in prospectively recruited adult patients with either lung or colorectal cancer, and pediatric patients with leukemia. We find that over half of the adult solid tumors show detectable rDNA rearrangements relative to either surrounding nontumor tissue or normal peripheral blood. In contrast, we find a greatly reduced frequency of rDNA alte...Continue Reading

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Citations

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