Abstract 4148: Role of the photoreceptor gene, CRX (cone-rod homeobox) in pathogenesis of non-WNT, non-SHH medulloblastoma

Abstract

Abstract Central nervous system (CNS) tumours are the second most common cancers diagnosed in children after leukemia and continue to be the leading cause of cancer-related mortality in children. Medulloblastoma (MB) is a highly malignant primary brain tumour that occurs in posterior fossa region of the brain. The current standard treatment regimen includes surgical resection, craniospinal irradiation and adjuvant chemotherapy. Although this has resulted in significant increase in survival, approximately one-third of medulloblastoma patients still die because of the disease. Genome-wide gene expression profiling studies have identified four molecularly distinct subgroups of medulloblastoma namely WNT, SHH, Group 3, and Group 4. Among the four subgroups, Group 3 patients exhibit highest incidence of metastasis and worst overall survival rates. Molecular mechanism underlying the pathogenesis of Group 3 medulloblastomas is not understood. Group 3 tumors often express retina photoreceptor-specific genes like CRX (Cone Rod Homeobox) which is a homeodomain transcription factor and it is essential for the normal development and maintenance of cones and rods cells of the retina. We have noted that this expression is also retained by the medulloblastoma cell lines like D425, D283 and D341 which have characteristics of Group 3 tumours. Downregulation of CRX in these cell lines brought about inhibition of cell proliferation and anchorage-independent growth as studied by soft agar colony formation assay. CRX gene, therefore, seems to act as an oncogene similar to OTX2, another homeobox gene overexpressed in medulloblastomas. Transcriptome profiling and CHIP-seq analysis is being carried out to identify genes regulated by CRX transcription factor to delineate the molecular mechanism underlying the oncogenic role of CRX in medulloblastoma pathogenesis. Citation Format: Shalaka Masurkar, Aliasagar Moiyadi, Epari Sridhar, Rakesh Jalali, Neelam Shirsat. Role of the photoreceptor gene, CRX (cone-rod homeobox) in pathogenesis of non-WNT, non-SHH medulloblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4148.