Targeting the epigenetics of NETs
Neuroendocrine Tumors (NETs) are a varied group of rare cancers which arise from the hormone-producing cells of the body’s nervous and endocrine systems. In this study, Dr Anna Karpathakis and the team at UCL ECMC investigate Genome-wide DNA methylation profiling of gastrointestinal NETs with an aim to lay the foundation for epigenetic treatments.
The NET BioBank, based at UCL, has an active patient cohort of over 800 patients from all over the UK. Due to the rarity of NETs and difficulty in obtaining fresh tissue and archival samples, very little is known about the (epi)genetic and germline mutations associated with these tumours. Tissue in this bank is used by researchers at the UCL ECMC to help identify new biomarkers for translation into diagnostics and therapeutics.
Epigenetics is the study of changes in gene activity which are not caused by changes in the DNA sequence. Most commonly, 'epigenetic' changes involve adding or removing chemical groups called methyl groups to DNA or proteins. Epigenetic marks such as DNA methylation in NETs of all origins and may be associated with worse prognosis. In recent years, it has become apparent that for many human diseases epigenetic drivers are key to pathogenesis and may have significant impact on clinical practice and patient management.
Dr Anna Karpathakis and the team at UCL ECMC investigate Genome-wide DNA methylation profiling of gastrointestinal NETs to identify increased methylation of mTOR, Wnt, and Notch pathways. Understanding of these epigenetic markers in this group of GI NETs patients could provide new therapeutic and imaging targets for these cancers and forge a new path for epigenetic treatments.
Karpathakis, A. et. al. J Clin Oncol 32, 2014 (suppl 3; abstr 212)
Karpathakis A et al., J Clin Cancer Res, 13, 2015