Discovering what ‘causes’ cancer has been a goal as elusive as hitting the Lottery by playing only the numbers in your birthdate. To complicate matters, most cases are unique events within themselves, adding a layer of heterogeneity that leads to even more hair-pulling frustration among researchers. However, cutting edge research has now revealed a possible origin for certain cancers, finding that “mutations causing epigenetic dysregulation can induce cancer on their own.”
A team led by Dr. Craig Thompson over at the Memorial Sloan-Kettering Cancer Center in New York is credited with the breakthrough in the understanding of cancer’s heterogeneity. According to co-author Altuna Akalin (Cornell University) the key inspiration behind this study was that “more than 50% of patients with chondrosarcomas exhibit gain-of-function mutations in either isocitrate dehydrogenase 1 (IDH1) or IDH2.” In their latest research, the group “performed genome-wide CpG methylation sequencing of chondrosarcoma biopsies.”
Here’s what they found:
- A targeted effect on the epigenome, where “IDH mutations were associated with DNA hypermethylation at CpG islands but not other genomic regions.”
- An intriguing biological function given that the “regions of CpG island hypermethylation were enriched for genes implicated in stem cell maintenance/differentiation and lineage specification.”
- Taking the finding one step further they performed a ‘reverse translation’ and showed that “in murine 10T1/2 mesenchymal progenitor cells, expression of mutant IDH2 led to DNA hypermethylation and an impairment in differentiation…”
- While putting the final nail in the coffin, they also showed that the effects “…could be reversed by treatment with DNA-hypomethylating agents.” This reversal is a pretty solid finding as it’s an indicator of causality.
The group concludes that: “Together, these data demonstrate that neomorphic IDH2 mutations can be oncogenic…” Finally, they showed that “the oncogenic potential of mutant IDH2 correlated with the ability to produce 2-hydroxyglutarate”, which leaves behind a biomarker with a lot of potential as well.
Get a jump-start on cancer’s epigenetic ways over at Genes & Development, October 2013