TERT promoter mutations, IDH mutations and 1p/19q co-depletion are surely promising markers to classify clinically heterogeneous cases of glioma. Among Grade-IV gliomas patients, however, Figure1 shows that triple-negative is surprisingly the second most common (17%) next to TERT mutations only (74%). It is also notable that triple-negative patients are composed of several histological types according to Table1; classical, mesenchymal, neural, or proneural. This implies the cell of origin can be different depending on each case. Furthermore, common acquired mutations are characterized by EGFR, PTEN, and NF1, which resemble molecular alternations in glioblastoma cases with wild type IDH (1).
Thus, I have major two questions to ask. Firstly, what kind of cell type corresponds to cancer stem-like cells in triple-negative gliomas, or whether trans-differentiation can occur in triple-negative glioma tissues (i.e. dedifferentiation from neural type to proneural)? Secondly, is metabolic reprogramming common in IDH-intact and triple-negative gliomas? If so, given that the metabolite 2-hydroxyglutarate inhibits histone demethylases and TET family 5-methylcytosine hydroxylases (2), genome-wide epigenetic modifications can be useful to classify triple-negative gliomas in more details.
1. Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas. The New England journal of medicine 2015.
2. Losman JA, Kaelin WG, Jr. What a difference a hydroxyl makes: mutant IDH, (R)-2-hydroxyglutarate, and cancer. Genes & development 2013;27:836-52.
I am greatly appreciated if you would give me some comment.
Dear Go,
I had a look on your RG profile and I am surprised by your interest in glioma because it does not seem to me that you published a lot in this domain.
But I am sure that you know the "big names" in the specific areas of your question.
I am referring to "Mitch" S. Berger (SF California; Scopus database: >600 publications; H94 and 35,000 citations) and to Michael Weller (Zürich Switzerland; SCopus database > 600 publications, H83, 36,000 citations).
Did you contact them?
Best regards
Robert
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