DIPG-50. CHROMATIN IMMUNOPRECIPITATION OF DIFFUSE INTRINSIC PONTINE GLIOMA TUMOR TISSUE IS FEASIBLE AND SHOW DIFFERENT ENRICHMENT COMPARED TO PRIMARY CELL LINE. Issue 2 (22nd June 2018)

• Record Type: Journal Article
• Authors: Kim, Yong Yean; Andricovich, Jaclyn; Yadavilli, Sridevi; Kambhampati, Madhuri; Tzatsos, Alexandros; Nazarian, Javad
• Is Part Of: Neuro-oncology. Volume 20:Issue 2(2018)supplement 2
• Page Start: i59
• Page End: i59
• Publication Date: 2018-06-22
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy059.143
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Diffuse intrinsic pontine glioma (DIPG) is the leading cause of mortality in pediatric central nervous system cancers. Histone mutations are found in >80% of DIPG cases. The most common mutation is histone 3.3 at position 27 resulting in lysine to methionine(H3.3K27M). This mutation results in epigenetic changes in methylation and acetylation of histones leading to aberrant change in transcription globally. Analysis of epigenetic changes via chromatin immunoprecipitation followed by sequencing (ChIP-Seq) has been performed in DIPG cell lines but not in tumor tissue. Culture conditions may not accurately reflect the epigenome of the tumor, thus we performed ChIP on three H3.3K27M mutant DIPG tumors (PID675, PID693, PID874). Checking enrichment by PCR revealed that the HOXA gene was enriched by tri-methylation at K27 (K27me3) and TOP3A was enriched by acetylation at K27 (K27ac), as expected. There was enrichment in both K27me3 and K27ac for GLI2. CDKN2A was enriched in K27me3 indicating down regulation in tumor tissue. However, in the DIPG primary cell line derived from PID675, CDKN2A was not enriched in K27me3 or K27ac and GLI2 was only enriched in K27ac. Given the difference seen between tumor tissue and cell line, our findings highlight the crucial importance of profiling the actual tumor tissue in DIPG.