RNA Methylation in Metabolically Disrupted Pediatric Cancers
Epigenetic changes, including methylation, are reversible chemical modifications that can affect gene expression. DNA, histones (the proteins that package the DNA) and RNA are subject to such modifications. Aberrant DNA and histone methylation have been clearly linked to cancer, however the impact of RNA methylation in cancers is poorly understood. In the present study, we propose that deregulation of RNA methylation is pervasive in cancers with mutations in energy metabolism genes.
To test this hypothesis, we propose to study a rare neuroendocrine cancer, paraganglioma, that arises as the result of an inherited mutation of a metabolic gene known as SDHB. Over 70% of children with metastatic paragangliomas have an inherited SDHB mutation and currently treatment options are limited. Studying the effects of SDHB mutation on RNA methylation may reveal novel markers of metastatic risk in these tumors. Moreover, findings of our research may be relevant to other cancers, especially those affecting metabolic genes. Importantly, the reversible nature of RNA methylation may shed light on the development of novel approaches to reverse the oncogenic effects of these epigenetic aberrations.