TRANSCRIPTOME AND METHYLOME PROFILES OF CNS GERM CELL TUMORS AND THEIR COMPARISON WITH TESTICULAR COUNTERPART

Abstract BACKGROUND: The pathophysiology of CNS germ cell tumors (GCTs) has yet to be fully unraveled, resulting in the paucity of treatment options. The biological comparison with its testicular counterpart has not been interrogated. METHODS: In total, 84 cases of CNS GCT were investigated for methylation and transcriptome analyses, and an integrative analysis of the normal cells undergoing embryogenesis and testicular GCTs was conducted. RESULTS: Transcriptome analysis revealed germinoma and non-germinomatous GCTs (NGGCTs) were clearly separated. On transcriptome, germinoma was characterized by primitive cell state, closely related to primordial germ cell (PGC) with meiosis/mitosis potentials. NGGCT had a feature of more differentiated cell state directed toward organogenesis. Germinoma was subdivided into two clusters on integrated transcriptome and methylation analysis, and they are different in the age distribution and tumor cell content. CNS and testicular GCTs were divided based on histology, either germinoma/seminoma or NGGCT/non-seminomatous GCTs on methylation. Expression analysis mainly clustered them depending on the site of origin and histology. CONCLUSIONS: Expression profiles of CNS GCTs distinctly reflect the histological variabilities. Germinoma may be clustered into two groups, with possible differentiation in treatment intensity in the future. GCTs at CNS and gonads seem to have a mutual cell-of-origin and similar genomic backgrounds, which potentiates site-agnostic treatment development.