GAS7 Deficiency Promotes Metastasis of MYCN-driven Neuroblastoma

Neuroblastoma (NB), the most common extracranial solid tumor in children, often metastasizes at a high rate. Here, we demonstrate that loss of function of the growth arrest-specific 7 gene (GAS7), located on Chr17p13.1, a deleted region in a subset of high-risk NB, accelerates dissemination of MYCN-overexpressing tumor cells in both zebrafish and xenografted mice models. Transcriptomic analysis of neuroblasotma tumors isolated from transgenic zebrafish overexpressing MYCN oncogene alone or MYCN with knockout of gas7 gene revealed that gene signitures affecting tumor cell-cell or cell-extracellular matrix interactions are significantly downregulated in tumors with gas7 loss of function. Our results provide the first genetic evidence that loss of function of a gene located in the Chr17p region contributes significantly to NB metastasis. Overall design: Examination of the transcriptomic profiles of neuroblastomas arose from transgenic fish overexpressing MYCN alone or MYCN with knockout of gas7.