Molecular Targeted Therapies of Childhood Choroid Plexus Carcinoma

Abstract : Choroid plexus carcinoma (CPC) is a rare malignant brain tumor originating from the epithelial cells lining the cerebral ventricles. CPC represents less than 0.6% of brain tumors in all age groups, yet is more frequent in children (2-4%), especially in infants under the age of 1, accounting for over 20% of brain tumors in this age group (1). The molecular events that drive the malignant progression of this tumor are not well understood, yet this knowledge is crucial to improve patient survival. Surgical resection combined with neo-adjuvant and/or adjuvant therapy remain the primary methods of treatment for CPC; however tumor progression and relapse is observed in 70% of cases (2). Despite improvements on the most current treatment protocols, long-term survival of CPC patients remains under 30% and survivors display significant neurocognitive and/or sensory deficits. (2,3). Identifying altered genes that drive the progression of CPC will refine current diagnostic and prognostic classifications of CPC patients, and promote the implementation of targeted therapies to improve patient survival and reduce long-term side effects. The proposed research aims to identify genetic lesions involved in CPC tumorigenesis in order to implement their use as unique markers for diagnostic and prognostic classification of choroid plexus tumor patients, as well as to promote the creation of personalized molecular targeted therapies. I hypothesize that recurrent genetic lesions accompanied by a significant change in gene expression in CPC, will be drivers of tumorigenesis in this malignant brain tumor. Consequently, this research project will seek to answer the following question: What genes may be used as molecular markers for diagnostic and prognostic classification of CPC, and for which tumor-promoting alterations could CPC therapies be created?