Abstract
INTRODUCTION
Childhood thalamic gliomas are rare cancers, accounting for 5% of all pediatric brain tumors and are of glial origin. The recent WHO classification places thalamic tumors in the category of midline gliomas based on discoveries that indicate histone 3 mutations as the driver genomic aberration of these cancers. Thalamic lesions may be confined to one side, spread to both thalami or to the brainstem. Despite variations in anatomical manifestation, the molecular events dictating tumor spread and pathogenesis are not well defined.
METHODS
A cohort of 294 specimens representing 207 subjects diagnosed gliomas with involvement of thalamus, were selected for methylation and whole genome sequencing using Illumina HIseq and EPIC bead array chips. Histological and clinical characterizations were correlated with molecular data to define unique pathways associated with tumor anatomical manifestation.
RESULTS
Histological analysis indicated the presence of histone mutation in 46% of specimens. IHC based WHO grading indicated 44% (91/207) of patients with Grade 4, 21% (44/207) were Grade 3, 3% (6/207) were Grade 2, 22% (45/207) were Grade 1 and 10% were other types (e.g. ganglioglioma). Methylation studies conferred hypomethylation to be associated with H3 mutation status. Median age at diagnosis was 9.8 years and 56% of the cohort was male. The presence of the H3K27M mutation was associated with lower survival despite tumor grade. Molecular studies are underway to decipher specific pathways associated with LGG, HGG and TGs.