A detailed analysis of the epigenetics factors controlling when and in what tissues genes are expressed of Wilms tumor reveals striking similarities to stem cells normally found in fetal kidneys. These findings by Massachusetts General Hospital (MGH) Cancer Center researchers have revealed new cellular pathways that are critical for Wilms tumor development and may also apply to other pediatric cancers. The report appears in the June 4 Cell Stem Cell.
Genetic mutations changes to the sequence of DNA molecules are known to underlie many types of cancer. But the role of epigenetics in tumor development is just beginning to be explored. The MGH team has been using advanced sequencing technology to investigate the role of chromatin, the structure that makes up chromosomes and consists of DNA wrapped around a protein backbone studded with molecules that can activate or suppress gene expression.
"An organism has only one genome, but it has many epigenomes because different cell types organize their genome into chromatin in ways that allow them to express just the right set of genes," explains Bradley Bernstein, MD, PhD, of MGH Pathology and the MGH Cancer Center, senior author of the study. Earlier studies from Bernstein's team used cutting-edge sequencing technologies to identify chromatin structures characteristic of embryonic stem cells. They observed active versions of chromatin structures termed "domains" at genes with critical developmental functions and saw features of both active and repressed chromatin at "bivalent" genes that were not currently expressed but maintained the potential for activation.
For the current study, Bernstein teamed with Miguel Rivera, MD, and Daniel Haber, MD, PhD, of the MGH Cancer Center, along with Aviva Presser Aiden, PhD, of the Broad Institute, to apply those powerful genomic technologies to cancer. The researchers chose to examine the epigenetics of Wilms tumor, a kidney cancer that
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Massachusetts General Hospital