K27/G34 versus K28/G35 in histone H3-mutant gliomas: A note of caution

Excerpt

The discovery of H3F3A mutations in pediatric gliomas [11] marked a milestone in understanding the pathogenesis of these tumors. Schwartzentruber et al. demonstrated that so-called H3.3K27M and H3.3G34R/V alterations serve as driver mutations in pediatric glioblastomas. Further investigations revealed that G34R/V mutations are seen mainly in hemispheric glioblastomas. In contrast, neoplasms with histone H3K27M mutations are often located in midline structures. An important example is the diffuse intrinsic pontine glioma (DIPG), with a median overall survival of less than 12 months [5]. The discovery of the above as well as H3.3K27I, H3.1K27M and H3.2K27M [2] mutations proved not only to be of major diagnostic and prognostic relevance [1] but also as a potential therapeutic target [9]. In fact, the correlation of H3K27M mutations with poor overall survival has led to the introduction of a new entity, the “diffuse midline glioma H3K27M-mutant”, in the updated “WHO Classification of Tumours of the Central Nervous System” (2016) [8]. …