Deciphering the Structural and Molecular Effects of a Novel Genetic Mutation by In Silico Analysis in Chordoma Cell Line

Abstract Chordoma is a rare bone tumor that is considered to have originated from the remnants of notochord by the general consensus in the field. Chordoma patients suffer from local invasion and recurrence of the disease, along with high resistance to conventional therapies. Despite the scarcity of the disease, new biomarkers must be discovered to develop targeted therapeutics. This study aimed at analyzing the whole exome sequencing data of a chordoma cell line, CH22, which held more than 3,000 missense variants in the genome. These missense-carrying genes were investigated in terms of their association with chordoma pathogenesis. Out of them, neurotrophic tyrosine kinase receptor type 3 (NTRK3) and nuclear factor erythroid 2-related factor 2 were found to be associated with the altered pathways involved in chordoma. Further examination through structural modeling, molecular docking, and phylogenetic analyses related to the missense variants of NTRK3 was conducted in the scope of this study.