Tumor to normal single-cell mRNA comparisons reveal a pan-neuroblastoma cancer cell
Kildisiute, Gerda; Kholosy, Waleed M.; Young, Matthew D.; Roberts, Kenny; Elmentaite, Rasa; van Hooff, Sander R.; Pacyna, Clarissa N.; Khabirova, Eleonora; Piapi, Alice; Thevanesan, Christine; Bugallo-Blanco, Eva; Burke, Christina; Mamanova, Lira; Keller, Kaylee M.; Langenberg-Ververgaert, Karin P.S.; Lijnzaad, Philip; Margaritis, Thanasis; Holstege, Frank C.P.; Tas, Michelle L.; Wijnen, Marc H.W.A.; van Noesel, Max M.; del Valle, Ignacio; Barone, Giuseppe; van der Linden, Reinier; Duncan, Catriona; Anderson, John; Achermann, John C.; Haniffa, Muzlifah; Teichmann, Sarah A.; Rampling, Dyanne; Sebire, Neil J.; He, Xiaoling; de Krijger, Ronald R.; Barker, Roger A.; Meyer, Kerstin B.; Bayraktar, Omer; Straathof, Karin; Molenaar, Jan J.; Behjati, Sam
(2021) Science advances, volume 7, issue 6, pp. 1 - 13
(Article)
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).
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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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Keywords: General
ISSN: 2375-2548
Publisher: American Association for the Advancement of Science
Note: Funding Information: Informed consent for research was obtained from participants (or their carers). Studies underlying this paper have received appropriate approval by ethics review boards as per national legislation. Dutch tumor samples were obtained through an institutionally approved research study. U.K. tumor samples were collected under the following studies: National Health Service (NHS) National Research Ethics Service reference 16/EE/0394 (tumor samples) and NHS National Research Ethics Service reference 96/085 (fetal tissues). Additional fetal tissue was provided by the Joint Medical Research Council (MRC)/Wellcome Trust–funded (grant #099175/Z/12/Z) Human Developmental Biology Resource (HDBR; www.hdbr.org) (10), with appropriate maternal written consent and approval from the Newcastle and North Tyneside NHS Health Authority Joint Ethics Committee. HDBR is regulated by the U.K. Human Tissue Authority (HTA; www.hta.gov.uk) and operates in accordance with the relevant HTA Codes of Practice. Funding Information: This study was funded by the Wellcome Trust (references 110104/Z/15/Z, 206194, 211276/Z/18/Z, 211276/C/18/Z, 102803/Z/13/Z, and 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. Publisher Copyright: 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).
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