Abstract P77: DISCOVERY OF NEW FACTORS INVOLVED IN MEDULLOBLASTOMA DEVELOPMENT AND INVESTIGATION OF ITS REGULATORY MECHANISM

Medulloblastomas, which occurs most commonly in children, is defined as an embryonal tumor derived from cells in the early stages of development. However, it is still unclear whether these embryonal tumors arise from embryonic cells in the uterus or as a result of single oncogenic event in fetal cells that rapidly progress to genetic instability. Meanwhile, potential transcription factor ZNF536 is most abundant in brain, especially in developing central nervous system. ZNF536 has been reported to have an inhibitory effect on neuronal differentiation, but the detailed regulatory mechanism has not been revealed. In particular, its pathological function in tumor development or progression of tumors is unknown. In this study, spontaneous tumor formation was observed in Zfp536+/- heteromice about 1 year old, and knock-down of ZNF536 in normal neuronal cells led cancerous phenotypes, such as neurosphere formation. Additionally, when comparing RNA expression levels in molecular genetic subgroups of medulloblastoma, ZNF536 expression was observed to be significantly reduced in group3, which is known to have the most malignant medulloblastoma. Based on our observation that loss of ZNF536 expression led spontaneous cancer development, we investigated the effect on cancer phenotypes after ZNF536 modulation. Besides, by performing ChIP-sequencing and RNA-sequencing, we identified the several downstream candidate targets of ZNF536 and further demonstrated comprehensive mechanisms of ZNF536 involved in cancer development. In summary, we suggested new factors including ZNF536 as a regulator of medulloblastoma development and progress, also we demonstrated regulation mechanisms by ZNF536. These results will provide insights understanding medulloblastoma development and new targeting strategies. Citation Format: Eun-Jin Yun and Seung Tae Baek. DISCOVERY OF NEW FACTORS INVOLVED IN MEDULLOBLASTOMA DEVELOPMENT AND INVESTIGATION OF ITS REGULATORY MECHANISM [abstract]. In: Proceedings of Frontiers in Cancer Science 2024; 2024 Nov 13-15; Singapore. Philadelphia (PA): AACR; Cancer Res 2025;85(15_Suppl):Abstract nr P77.