Transcriptomic analysis of cell-of-origin CNS neuroblastoma, FOXR2 activated [Multiome]

The transcription factor FOXR2 is the universal driver of childhood central nervous system neuroblastoma, FOXR2 activated (NB-FOXR2). NB-FOXR2 tumors arise exclusively in the brain hemispheres, and despite morphological similarities to other pediatric brain tumors, they are a molecularly distinct entity based on DNA methylation profiling. The cell-of-origin is unknown. Here, we profiled a cohort of rare NB-FOXR2 tumors by bulk and single-cell transcriptomics. Through systematic comparative analyses, we delineate tumor transcriptional states and candidate cell-of-origin. More broadly, we demonstrate systematic molecular profiling of childhood cancers to orient oncogenic targeting for in vivo modeling, a critical resource for the study of rare tumors and development of therapeutics. 3 genetically-engineered In utero electroporation mouse model with brain tumor sequenced for single-cell multiome. All the samples have a Foxr2 induced overexpression and one has also a p53 loss of function. The 3 scMultiome samples have been split into 2 parts (RNA-seq and ATAC-seq; 6 sample records). Each raw data fastq file is specific to one data type only. However, the processed files contain information for both RNA-seq and ATAC-seq in the same file (as indicated in the sample description field).