RNA sequencing identifies key differences in patient derived xenograft models of primary and metastatic pediatric neuroendocrine tumors

Here we report the RNA sequence of a primary patient-derived xenograft neuroendocrine tumor and compare it to the RNA sequence of an intraperitoneal metastatic tumor that was established using the respective primary tumor. Using this data, we identified key differences that validated the metastatic tumor to indeed have a more mestatic genotype. Noteworthy differences were the upregulation of matrix metalloproteinases and downregulation of PTK2, both associated with metastatic neuroendocrine tumors in patients. Furthermore, we found upregulated pathways that could potentially be targeted through small molecule inhibition. One such example is ERK1/2 had a higher expression in the metastatic tumor and using a MEK inhibitor, were able to successfully deplete metastasis of the tumor in an in vivo model. These data will be helpful in translating the therapeutics tested to a clinical arena. Overall design: Examination of RNA in a primary versus a metastatic pediatric neuroendocrine patient-derived xenograft tumor.