Abstract A32: A specific antibody for Histone H3 Lys27Met mutation for the characterization of pediatric glioblastomas

Abstract

Abstract Pediatric gliomas such as glioblastoma multiforme (GBM) and diffuse intrinsic pontine glioma (DIPG) are aggressive brain tumors for which there is no effective therapy. The reason for the poor therapeutic outcome for children diagnosed with glioblastomas might be due to the therapeutic approach, which is not significantly different from the treatment of adult gliomas. Recent studies have shown that the gene expression profile of pediatric gliomas is distinct from histologically similar tumors in adults. These findings strongly suggest that the underlying mechanisms of tumor progression are different in these gliomas. Whole-genome sequencing of these pediatric tumors has revealed mutations in genes of H3F3A and HIST1H3B encoding histone H3.3 or H3.1, respectively. The mutations resulted in a substitution of lysine (K) to methionine (M) at position 27 of the protein (H3K27M). The lysine 27 residue of histone H3 is a posttranslational modification site, methylated by the polycomb repressive complex 2 (PRC2). A mutation like H3K27M might play a significant role in tumorigenesis and tumor progression since histones and their posttranslational modifications are key epigenetic regulators. In collaboration with the laboratory of David Allis, we raised antibodies against the K27M mutation of histone H3. Using this antibody, Lewis et al. corroborated the presence of H3 K27M protein in DIPG samples containing the mutant allele. Furthermore, they provided evidence that this mutation can alter the molecular processes in the nucleus through a gain-of-function mechanism in glioblastoma. Here we show that this Anti-Histone H3, K27M mutant antibody (Cat. No.: ABE419), together with other modified histone antibodies, are useful tools for the characterization and classification of different type of brain tumors and can be used in several applications including immunoblotting and chromatin immunoprecipitation (ChIP). Citation Format: Anita Lozsa, Robin T. Clark, Peter W. Lewis, Matthew S. Koletsky, Oren J. Becher, John Rosenfeld, Sturges Michael, David C. Allis, Trinette Chuang, Wayne Speckmann, Alejandra Solache. A specific antibody for Histone H3 Lys27Met mutation for the characterization of pediatric glioblastomas. [abstract]. In: Proceedings of the AACR Special Conference on Pediatric Cancer at the Crossroads: Translating Discovery into Improved Outcomes; Nov 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;74(20 Suppl):Abstract nr A32.