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

Gerda Kildisiute, Waleed M Kholosy, Matthew D Young, Kenny Roberts, Rasa Elmentaite, Sander R van Hooff, Clarissa N Pacyna, Eleonora Khabirova, Alice Piapi, Christine Thevanesan, Eva Bugallo-Blanco, Christina Burke, Lira Mamanova, Kaylee M Keller, Karin P S Langenberg-Ververgaert, Philip Lijnzaad, Thanasis Margaritis, Frank C P Holstege, Michelle L Tas, Marc H W A WijnenMax M van Noesel, Ignacio Del Valle, Giuseppe Barone, Reinier van der Linden, Catriona Duncan, John Anderson, John C Achermann, Muzlifah Haniffa, Sarah A Teichmann, Dyanne Rampling, Neil J Sebire, Xiaoling He, Ronald R de Krijger, Roger A Barker, Kerstin B Meyer, Omer Bayraktar, Karin Straathof, Jan J Molenaar, Sam Behjati

Research output: Contribution to journalArticlepeer-review

60 Citations (Scopus)

Abstract

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 a pan-neuroblastoma cancer cell state exists, which may be attractive for novel immunotherapeutic and targeted avenues.

Original languageEnglish
Article numbereabd3311
JournalScience advances
Volume7
Issue number6
DOIs
Publication statusPublished - Feb 2021

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