Paper

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

Duncan, Catriona, Burke, Christina, Piapi, Alice, Margaritis, Thanasis, He, Xiaoling, Barker, Roger A, Young, Matthew D, Blanco, Eva Bugallo, Wijnen, Marc Hwa, Teichmann, Sarah A, Frank Cp Holstege, Behjati, Sam, Barone, Giuseppe, Haniffa, Muzlifah, De Krijger, Ronald R, Tas, Michelle L, Ignacio Del Valle, Van Hooff, Sander R, Roberts, Kenny, Van Der Linden, Reinier, Molenaar, Jan J, Khabirova, Eleonora, Van Noesel, Max M, Kildisiute, Gerda, Anderson, John, Bayraktar, Omer, Elmentaite, Rasa, Lira Mamanova, Sebire, Neil J, Kholosy, Waleed M, Meyer, Kerstin B, Straathof, Karin, Lijnzaad, Philip, Rampling, Dyanne, Thevanesan, Christine, Achermann, John C

2020

Overview

Abstract Neuroblastoma is an embryonal childhood cancer that arises from aberrant development of the neural crest, mostly within the fetal adrenal medulla. 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=16,591) with 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 652 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 an attractive target for novel therapeutic avenues. Competing Interest Statement The authors have declared no competing interest.

• Publisher: Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
• Subject: Adrenal medulla / Cancer / Cancer Biology / Children / Fetuses / Genomes / Neural crest / Neuroblastoma / Neuroblastoma cells / Phenotypes / Transcription