Epigenetics and cancer
Epigenetic control of gene expression is mediated by a variety of mechanisms including DNA methylation and histone modifications. In normal development, such mechanisms are crucial for gene expression programmes that determine cell-fate. In cancer, there is increasing evidence that aberrant epigenetic regulation is a key component in the evolution of the cancer cell. As many epigenetic modifications are enzymatically regulated and reversible, correcting epigenetic defects in cancer cells pharmaceutically represents an exciting opportunity for treating cancer. In addition, epigenetic marks can also be detected with relative ease, and are therefore also excellent potential biomarkers.
In Bristol we are utilising genome-wide methylation analysis to identify tumour-suppressor genes and oncogenes in childhood tumours such as Wilms' tumour and neuroblastoma. The cartoon shown on the right depicts Wilms' tumour specific detection of high DNA methylation at a region on chromosome 5q31, which corresponds to a family of paralogous protocadherin genes. Thus protocadherins were identified as putative Wilms' tumour suppressor genes. The downstream effects of such epigenetic silencing, for example signalling pathways affected is also being investigated, together with possible upstream determinants of epigenetic aberrations.
Research in Nuclear Dynamic Laboratory (Abder Kaidi) applies cell imaging and next generation sequencing approaches to identify cancer associated changes in nuclear structure and chromatin organisation (both linked to epigenetics). These are being harnessed as potential biomarkers for diagnosis and as novel therapeutic targets.