Wednesday, July 10, 2013

The Story with Gliomas and Backtracking Literature

A few days ago, I attended a great talk here at MSKCC by Timothy Chan on gliomas. Gliomas are tumors of the brain or spine that arise from glial cells, and (according to Wikipedia) make up about 30% of CNS tumors.

OK, so why was the talk so interesting? Well, I didn't know anything about gliomas before, and now I do. One of the things I learned is that many gliomas seem to have the same pair of enzymes (IDH1/IDH2) mutated. It is well-known now (but not a few years ago) that one consequence of these mutations is that the mutant IDH's produce 2-hydroxyglutarate (2-HG), instead of alpha-ketoglutarate. OK, gibberish gibberish, what does it mean? Well, 2-HG does a lot of bad stuff in the cell, and seems to be implicated in tumor progression. Most notably (to me), it seems to activate/inhibit a bunch of enzymes involved in methylation and demethylation, which eventually cause what Dr. Chan calls "epigenetic chaos." The epigenome of these gliomas just looks totally screwed up in comparison to the epigenome of normal, non-cancerous cells.

Again, so what? Well, the epigenome is what you might imagine as a very high-level form of regulation. Epigenetic marks on DNA can silence or upregulate the expression of genes. Aside from the really fascinating link between metabolism and epigenetics here, what really dazzled me about Chan's talk was that it led me to re-evaluate everything I have been reading as a new postdoc. I have a paper tacked to the wall of my cube titled "Cancer mistunes methylation," and while it is heavily annotated and marked up with my notes, I'm surprised to find that after Chan's talk, I need to go back and read again. And that is the mark of a great talk; I realize that everything I thought I understood, I really didn't. And now here I go down the rabbit-hole.

1 comment:

  1. just had a look at the paper you mentioned and now am quite surprised to see the sink analogy is so widely picked up (Fig 1, bottom right) -- would be a nice name for the next software tool :)