Published in:
Open Access
01-12-2014 | Research article
The nucleolar size is associated to the methylation status of ribosomal DNA in breast carcinomas
Authors:
Maria Giulia Bacalini, Annalisa Pacilli, Cristina Giuliani, Marianna Penzo, Davide Treré, Chiara Pirazzini, Stefano Salvioli, Claudio Franceschi, Lorenzo Montanaro, Paolo Garagnani
Published in:
BMC Cancer
|
Issue 1/2014
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Abstract
Background
There is a body of evidence that shows a link between tumorigenesis and ribosome biogenesis. The precursor of mature 18S, 28S and 5.8S ribosomal RNAs is transcribed from the ribosomal DNA gene (rDNA), which exists as 300–400 copies in the human diploid genome. Approximately one half of these copies are epigenetically silenced, but the exact role of epigenetic regulation on ribosome biogenesis is not completely understood. In this study we analyzed the methylation profiles of the rDNA promoter and of the 5’ regions of 18S and 28S in breast cancer.
Methods
We analyzed rDNA methylation in 68 breast cancer tissues of which the normal counterpart was partially available (45/68 samples) using the MassARRAY EpiTYPER assay, a sensitive and quantitative method with single base resolution.
Results
We found that rDNA locus tended to be hypermethylated in tumor compared to matched normal breast tissues and that the DNA methylation level of several CpG units within the rDNA locus was associated to nuclear grade and to nucleolar size of tumor tissues. In addition we identified a subgroup of samples in which large nucleoli were associated with very limited or absent rDNA hypermethylation in tumor respect to matched normal tissue.
Conclusions
In conclusion, we suggest that rDNA is an important target of epigenetic regulation in breast tumors and that rDNA methylation level is associated to nucleolar size.