Human-specific genes define human-specific cancer cell populations in medulloblastoma

While being studied as potential drivers of human brain development, the impact of human-specific (HS) genes on disease remains unclear and their functional role in tumor development has never been demonstrated. Here we analyzed the expression of HS genes in human medulloblastoma, and we found that HS genes are predominantly expressed in medulloblastoma cells with a gene signature similar to cells of human developing cerebellum, in particular related to glutamatergic lineage and Rhombic Lip (RL). Interestingly, the human developing RL displays unique features compared to mice and macaques, such as the RLsvz that is also believed to contain the cell of origin of group3 and 4 medulloblastoma. Here we characterized the medulloblastoma cells that express the HS gene POMZP3 that revealed a significant gene enrichment for the RLsvz cells. Furthermore, the POMZP3 in co-expression with c-MYC in mice is also able to generate medulloblastoma. Our results suggest that HS genes can define cancer cell populations and could have a functional role in cancer development.