Astrocytoma Genomics

26 Mar

I’ve been reading lots of articles regarding new developments in terms of brain cancer treatment.  Most allude to the different genetic types of Glioblastoma Multiforme (GBM) tumors, but none have really delved into what these mutations are/ mean.  So, I went and purchased ‘The biology of Cancer‘ by Robert A. Weinberg.  It provided a great overview and in-depth explanation of what is known and theories to be tested.  Unfortunately, it did not go deeply into the area of brain cancer that I am most interested in.  So, I did more searching and came upon the Current Opinion in Genetics & Development journal, which included such an article written by doctors at Johns Hopkins University.  You can find the article on the Science Direct website at:

This article is an excellent genetic primer on Astrocytoma/ GBM tumors.  It does highlight the progress that has been made to better classify these tumors based on genetics, specifically proneural (IDH1/2), classical (EGFR) or mesenchymal (NF1).  The article also highlights, as I have suspected, that most GBM tumors have cells belonging to each of the proposed subtypes.  Of which, there is even more heterogeneity with proneural tumors, resulting in divergent outcomes based on wild-type versus mutant.

AstrocytomaGenetics

As to treatments, it touched upon some of the targeted research against IDH1-R132H mutant tumors, specifically selective inhibitors.  Some examples mentioned include observations related to Decitabine treatments and active Clinical Trials like NCT02193347.  The article did mention about challenges related to similar research for classical GBM tumors, like immunosuppression and tumor evolution.  Therefore, we are seeing significant alternative research like tumor-specific antigen vaccines.

The references and recommended reading list is quite lengthy.  The article highlights which ones are of special interest and of outstanding interest.  Next on my reading list will be:

  • Parsons DW, Jones S, Zhang X, Lin JC, Leary RJ, Angenendt P, Mankoo P, Carter H, Siu IM, Gallia GL et al.: An integrated genomic analysis of human
  • Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, Kos I, Batinic-Haberle I, Jones S, Riggins GJ et al.: IDH1 and IDH2 mutations in gliomas. N Engl J Med 2009, 360:765-773.
  • Champiat S, Ferte C, Lebel-Binay S, Eggermont A, Soria JC: Exomics and immunogenics: bridging mutational load and immune checkpoints efficacy. Oncoimmunology 2014, 3:e27817.