AANS, California, United States Of America, 13 - 17 April 2019, pp.1
Chromatin Modifier Alterations Are Very Common But Mostly Random in Diffuse Gliomas
Özduman K*, Ülgen E, Can Ö, Erşen Danyeli A, Akyerli-Boylu C, Bilguvar K, Pamir MN
All of the current molecular-markers used for group gliomas are Chromatin Modifiers (CM). Based on this observation we hypothesized that other chromatin modifiers with clinical correlation may be present in diffuse gliomas and analyzed a cohort for genetic alterations in CM genes.
27 hemispheric diffuse gliomas (Median age 48, range 20-76) and paired blood samples were Whole Exome Sequenced and 1-somatic non-synonymous single nucleotide variations, 2- homozygous deletions and high-level amplifications, 3-germline risk single nucleotide polymorphisms were identified. Different molecular subsets were identified (6 IDH-only, 12 TERT-only, 3 H3.3-mutant and 6 triple-negative). A manually curated list of 195 CM genes was analyzed for the above genetic alterations. Findings were analyzed against age, glioma molecular subset, WHO-grade and histopathology.
61(31.3%) out of the 195 curated genes were altered. At least one chromatin modifier was somatically altered in 27/27(100%) of the patients. Chromatin modifier alterations were significantly enriched in gliomas (p=6.22e-22; hypergeometric gene set enrichment testing). Alterations were heterogeneously distributed among samples. Only 18/61 of the alterations were observed in more than 1 patient sample. No novel and recurrent alterations were observed (other than IDH, ATRX, PTEN, SMARCA4, H3F3A). Age had no effect on the distribution of the chromatin modifiers in the sample set. Highest number of CM were observed in the IDH-mutant subset (Median IDH: 5, TERT-only:1.5, H3.3-mutant:3, triple-negative 3. Difference non-significant). No significant differences were observed for WHO grade or histopathology.
CM alterations are very common but mostly random in diffuse gliomas. No previously unknown, recurrent CM of clinical significance was identified.