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

Lookup NU author(s): Professor Muzlifah Haniffa

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).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.

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Author(s): Kildisiute G, Kholosy WM, Young MD, Roberts K, Elmentaite R, van Hooff SR, Pacyna CN, Khabirova E, Piapi A, Thevanesan C, Bugallo-Blanco E, Burke C, Mamanova L, Keller KM, Langenberg-Ververgaert KPS, Lijnzaad P, Margaritis T, Holstege FCP, Tas ML, Wijnen MHWA, van Noesel MM, del Valle I, Barone G, van der Linden R, Duncan C, Anderson J, Achermann JC, Haniffa M, Teichmann SA, Rampling D, Sebire NJ, He X, de Krijger RR, Barker RA, Meyer KB, Bayraktar O, Straathof K, Molenaar JJ, Behjati S

Publication type: Article

Publication status: Published

Journal: Science Advances

Year: 2021

Volume: 7

Issue: 6

Online publication date: 05/02/2021

Acceptance date: 18/12/2020

Date deposited: 26/10/2023

ISSN (electronic): 2375-2548

Publisher: American Association for the Advancement of Science

URL: https://doi.org/10.1126/sciadv.abd3311

DOI: 10.1126/sciadv.abd3311

PubMed id: 33547074

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