Student Presenter(s): Brightlyn Kwa, Siddhi Modi
Faculty Mentor: Haotian Zhao
Department: Biomedical Sciences
School/College: College of Arts and Sciences, Long Island

Choroid plexus carcinoma (CPC) is a rare and aggressive brain cancer that primarily affects children. The benign forms of CPC are choroid plexus papilloma (CPP) and atypical CPP. While little is known about CPC, the cancer phenotype includes CPC cells with solitary cilia instead of multi-ciliated cells (MCCs), persistent TP53 mutations, and disruptions to the multi-ciliogenesis program that is led by GMNC-MCIDAS transcription factors. MCCs can be found in the ependyma and choroid plexus (CP) epithelia, where the CP secretes cerebrospinal fluid and the ependymal cilia circulate it throughout the ventricular system. In mice models, MCCs had cilia defects due to the deletion of Trp53 and Rb1, paralleling the defects in the human GMNC-MCIDAS pathway. Geminin Coiled-Coil Domain Containing (GMNC) and multi-ciliate differentiation and DNA synthesis associated with cell cycle protein (MCIDAS) aid in early MCC differentiation, triggered by NOTCH inhibition. It is found that abnormal NOTCH signaling led to the development of CPPs. In this study, we show that faulty NOTCH and Sonic Hedgehog signaling in mice leads to tumors similar to human CPC tumors. NOTCH drives tumor development as it inhibits GMNC and MCIDAS expression, yielding monociliated cells. However, the overexpression of Gmnc-Mcidas yields viable results as multiplication reoccurs and tumor proliferation decreases. Mastering the GMNC-MCIDAS program and its role in inhibiting tumorigenesis leaves room for treatment options for CPC.