Abstract 1356: Frequent H3F3A K27M mutations in thalamic gliomas from young adult patients

Abstract

Abstract Introduction. Mutations in the H3F3A gene, which encodes histone H3.3, were recently reported in cases of pediatric glioblastoma. H3F3A K27M mutations occur in gliomas that arise at midline locations, including the pons, thalamus, and spine; moreover, this particular mutation is found mainly in tumors in children and adolescents. In this study, we aimed to determine the association between H3F3A mutations and adult thalamic glioma. Methods. Genomic H3F3A was sequenced from 20 separate thalamic gliomas. Of the 20 tumors, 18 were high-grade thalamic gliomas, and of these 18, 11 were from patients under 50 years of age (median age, 38 years; range, 17 - 46), and seven were from patients more than 50 years of age. Additionally, for 14 of the 20 gliomas, 639 genes_including cancer-related genes and chromatin-modifier genes_were sequenced, and the Infinium HumanMethylation450K BeadChip was used to examine DNA methylation across the genome. Results. The H3F3A K27M mutation was present in 10 of (91%) of the 11 younger patients, and absent from all seven older patients. Additionally, H3F3A K27M was not detected in the two diffuse astrocytomas. By additional sequencing, recurrent mutations were identified in TP53, ATRX, NF1, and EGFR. In addition, a KDM6A mutation was found in one case of diffuse astrocytoma and a CREBBP mutation was identified in one case of glioblastoma with the H3F3A K27M mutation. Gliomas with H3F3A K27M from pediatric or young-adult patients had similar, characteristic DNA methylation profiles. In contrast, thalamic gliomas with wild-type H3F3A had DNA methylation profiles similar to those of hemispheric glioblastomas. Conclusion. We found that high-grade thalamic gliomas from young adults, like those from children and adolescents, frequently have the H3F3A K27M mutation. Citation Format: Akitake Mukasa, Koki Aihara, Kengo Gotoh, Kuniaki Saito, Genta Nagae, Shingo Tsuji, Kenji Tatuno, Shogo Yamamoto, Shunsaku Takayanagi, Yoshitaka Narita, Soichiro Shibui, Hiroyuki Aburatani, Nobuhito Saito. Frequent H3F3A K27M mutations in thalamic gliomas from young adult patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1356. doi:10.1158/1538-7445.AM2014-1356