01 July 2016
An international team of researchers, including Garvan’s Professor Susan Clark and colleagues, has shown that DNA methylation analysis is a mature technology that is ready for clinical use. The researchers’ study underscores the robustness of DNA methylation and other epigenetic tests, and heralds an era in which epigenetics will be used in clinical diagnostics and personalised medicine.
‘Epigenetics’ refers to chemical modifications that ‘decorate’ DNA and its associated proteins. Epigenetic modifications control gene activity independently of the genetic code, so that they comprise an additional ‘layer’ of information and control that overlies the genome itself. DNA methylation is one form of epigenetic modification.
In many diseases, including cancer, the epigenetic control of the genome is heavily distorted. By measuring these alterations, a detailed picture of disease-specific changes emerges, which can help distinguish disease subtypes or identify suitable treatments. To date, however, little epigenetic testing has been carried out in the clinic.
Prof Clark says, “What we wanted to do in this study was to carry out a wide-ranging technology comparison – to look in detail at the many DNA methylation tests (assays) now in existence, and to compare their accuracy and robustness in a systematic fashion.”
The research was coordinated by the Research Center for Molecular Medicine of the Austrian Academy of Sciences (CeMM; Vienna) and included contributions from 18 research groups across three continents.
Prof Clark’s team, which included Garvan researchers Dr Shalima Nair, Dr Clare Stirzaker, Dr Wenjia Qu and Aaron Statham, compared two DNA methylation tests they had previously optimised: amplicon bisulphite sequencing (AmpliconBS) and mass spectrometric analysis of DNA methylation (EpiTyper). Both assays have their roots in bisulphite-based methods developed by Prof Clark in the 1990s, which were quickly adapted as the gold standard at the time.
The study, which was published this week in Nature Biotechnology, found that AmpliconBS is the best choice for assaying dozens of genomic regions in parallel, while EpiTyper provides the highest sample throughput. It concludes that, overall, DNA methylation analysis is ready for widespread use in the clinic.
The study was published coordinately with three other papers in Nature Biotechnology and Nature Communications. Conducted in the context of the European Blueprint Project and the International Human Epigenome Consortium, the four papers together mark the feasibility of epigenetic analysis for clinical diagnostics and personalised medicine, in cancer and beyond.