LSD1 is a Potential Therapeutic Target in Medulloblastoma

The importance of epigenetic gene regulation has been established in medulloblastoma for both DNA methylation and histone acetylation. Histone methylation has long been considered to be irreversible and less versatile. With the recent discovery of the first histone demethylase, lysine desaminase 1 (LSD1), this paradigm has been overcome. Taken into consideration the high expression and functional importance of LSD1 in various other tumor types, including neuroblastoma (Schulte et al., Cancer Res 2009), we analysed the expression and functional implication of LSD1 in medulloblastoma. Re-analysis of microarray data and immunohistochemistry using a tissue microarray revealed high expression of LSD1 mRNA and protein levels in medulloblastoma as compared to human cerebellum. LSD1 was also highly expressed in human medulloblastoma cell lines. Medulloblastomas derived from PTCH+/- mice displayed high LSD1 mRNA expression compared to control tissue. Treatment of human medulloblastoma cell lines with the monamine oxidase inhibitor tranylcypromine, a small molecular inhibitor of LSD1, resulted in reduced cellular viability. We are currently analysing the functional role of LSD1 in medulloblastoma cells in vitro using siRNA mediated knock down and aim to elucidate the role of LSD1 in the pathogenesis of murine medulloblastoma using the transgenic medulloblastoma mouse models, PTCH+/- and SmoA1.