CTA: What can your epigenetic data tell us about other retinal diseases, such as age-related macular degeneration?

Dr Dyer: In the same way that genomic studies have transformed the cancer field, we’ve also learned a lot about genetic predisposition in the retinal degeneration field. There have been very large genomic studies looking for people who may have mutant alleles that might predispose them to different types of retinal degeneration or other retinal diseases.

One of the problems you have in those studies is historically, people would look at the genes themselves and see if there was a mutation or a variant in the coding part of the genome. But what our epigenetic data really provide is a road map for the non-coding part of the genome. If there is an enhancer, or some other really important regulatory region in the genome that controls retinal development or retinal homeostasis, researchers can go and look at this database that we’ve provided and look for mutations in the regulatory regions of the genome based on our epigenetic data.

What our study does is allows researchers to narrow that down to the key enhancers in other regulatory regions that may be mutated in other retinal diseases beyond retinoblastoma.

CTA: What are your next steps?

Dr Dyer: There are a couple of next steps. One is to use information from the window in development to go in at that time and find the actual cell of origin. The second is to extend the epigenetic profiling to all other pediatric cancers.

Ultimately, our goal is to identify vulnerabilities that can be exploited with molecular targeted therapy to improve outcomes and quality of life for children with cancer.

Reference

  1. Aldiri I, Xu B, Wang L, et al. The dynamic epigenetic landscape of the retina during development, reprogramming, and tumorigenesis. Neuron. 2017;94:550-68.