The lede was buried.

Disappointed in your crypto vote :(

Maybe not all mutations are exactly the same!

We are so grateful for the hard work of our students and trainees, and of our collaborators both at SDSU and in Germany, that allowed us to undertake this large and fun project! (6/6)

Via RNAseq, we see pro-tumor pathways turned on that have these R132Q-expressing tumors looking a little bit more like WT IDH1-driven gliomas, which typically are more aggressive and have worse outcomes. (5/6)

Cell lines expressing IDH1 R132Q have more D2HG than those expressing R132H...and mouse xenografts expressing R132Q have more D2HG in the tumors and sera, too. Tumors are bigger. (4/6)

We've been working a few years to try to figure this out, & our wonderful team of scientists w/ biochemical, computational, & cell biology expertise have showed that catalytic efficiency DOES matter! (3/6)

One of the catalytically weirdest mutants is R132Q -- it makes buckets of D2HG, especially compared to the more common mutations seen in patients, like R132H.
But does this catalytic efficiency translate to more D2HG in a cell? In a tumor? (2/6)