Profiling the Epigenetic Landscape of the Tumor Microenvironment Using Chromatin Immunoprecipitation Sequencing.

Cancer cells within a tumor exhibit phenotypic plasticity that allows adaptation and survival in hostile tumor microenvironments. Reprogramming of epigenetic landscapes can support tumor progression within a specific microenvironment by influencing chromatin accessibility and modulating cell identity. The profiling of epigenetic landscapes within various tumor cell populations has significantly improved our understanding of tumor progression and plasticity. This protocol describes an integrated approach using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) optimized to profile genome-wide post-translational modifications of histone tails in tumors. Essential tools amenable to ChIP-seq to isolate tumor cell populations of interest from the tumor microenvironment are also presented to provide a comprehensive approach to perform heterogeneous epigenetic landscape profiling of the tumor microenvironment.

Wild-type isocitrate dehydrogenase under the spotlight in glioblastoma.

Brain tumors actively reprogram their cellular metabolism to survive and proliferate, thus offering potential therapeutic opportunities. Over the past decade, extensive research has been done on mutant IDH enzymes as markers of good prognosis in glioblastoma, a highly aggressive brain tumor in adults with dismal prognosis. Yet, 95% of glioblastoma are IDH wild-type. Here, we review current knowledge about IDH wild-type enzymes and their putative role in mechanisms driving tumor progression. After a brief overview on tumor metabolic adaptation, we present the diverse metabolic function of IDH enzymes and their roles in glioblastoma initiation, progression and response to treatments. Finally, we will discuss wild-type IDH targeting in primary glioblastoma.