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Tumor to normal single cell mRNA comparisons reveal a pan-neuroblastoma cancer cell

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He, Xiaoling 
Behjati, Sam 


Neuroblastoma is a childhood cancer that resembles developmental stages of the neural crest. It is not established what developmental processes neuroblastoma cancer cells represent. Here, we sought to reveal the phenotype of neuroblastoma cancer cells by comparing cancer (n=19,723) with normal fetal adrenal single cell transcriptomes (n=57,972). Our principal finding was that the neuroblastoma cancer cell resembled fetal sympathoblasts, but no other fetal adrenal cell type. The sympathoblastic state was a universal feature of neuroblastoma cells, transcending cell cluster diversity, individual patients and clinical phenotypes. We substantiated our findings in 650 neuroblastoma bulk transcriptomes and by integrating canonical features of the neuroblastoma genome with transcriptional signals. Overall, our observations indicate that there exists a pan-neuroblastoma cancer cell state which may be attractive for novel immunotherapeutic and targeted avenues.



Child, Humans, Neural Crest, Neural Stem Cells, Neuroblastoma, RNA, Messenger, Transcriptome

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Science Advances

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American Association for the Advancement of Science
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Medical Research Council (MC_PC_17230)
This study was funded by the Wellcome Trust (references 110104/Z/15/Z, 206194 and 211276/Z/18/Z, 211276/C/18/Z, 209328/Z/17/Z). Additional funding was received from the St Baldrick’s Foundation (Robert J Arceci Award to S.B.), NIHR (Great Ormond Street Biomedical Research Centre), ERC-START grant PREDICT-716079, NWO-Vidi grant 91716482, H2020-iPC-826121 grant, and National Institute for Health Research (NIHR 146281) Cambridge Biomedical Research Centre