Evidence of H3 K27M mutations in posterior fossa ependymomas

Excerpt

Histone 3 (H3) K27M mutations are considered to be a genetic hallmark of diffuse midline gliomas, including high-grade astrocytomas and diffuse intrinsic pontine gliomas (DIPG) [3]. Similar to IDH-mutated gliomas in adults, these mutations are associated with alterations in the epigenetic profile of tumor cells, and are thought to represent a main driving factor in gliomagenesis [2, 8]. In diffuse midline gliomas, H3K27M mutations have been demonstrated to induce de–repression of pro-oncogenic transcription factors by global reduction of histone 3 K27 trimethylation (H3K27me3) [2, 8]. Reportedly, H3K27M mutations are exceedingly rare in tumors other than in diffuse midline gliomas [6, 7, 14]. The possibility of an H3K27M mutation occurring in other brain neoplasms cannot, however, be excluded a priori. We report here the very unexpected finding of H3K27M mutations in two Group A posterior fossa ependymomas (PF-EPN-A), an aggressive subgroup of tumors with relatively stable genomes and no well-characterized oncogenic driving event [9, 10]. …