Genome-wide methylation profiles in primary intracranial germ cell tumors indicate primordial germ cell origin of germinoma [Illumina]. Homo sapiens

The pathogenesis of intracranial germ cell tumors (iGCTs) is not yet fully uncovered despite exhaustive genomic analyses. By means of a genome-wide methylation analysis, we show that pure germinoma is characterized by global DNA low methylation, a unique epigenetic feature distinct from all other subtypes of iGCTs. The patterns of methylation strongly resemble that of primordial germ cells (PGC) at the migration phase, indicating the cells of origin. Unlike PGC, however, hypomethylation extends to LINE1 retrotransposon. Microdissected histologically and epigenetically distinct components of mixed-GCTs shared identical mutations in the MAPK or PI3K pathways, suggesting that the genetic alterations were likely to have occurred at the pre-implantation phase in early embryogenesis. Thus, we propose iGCTs are “Zygotoma”. Overall design: Bisulphite converted DNA from 77 samples were hybridized to the Illumina Infinium HumanMethylation450 Beadchip