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Lookup NU author(s): Professor Muzlifah Haniffa
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© 2021, The Author(s).Tumor cells may share some patterns of gene expression with their cell of origin, providing clues into the differentiation state and origin of cancer. Here, we study the differentiation state and cellular origin of 1300 childhood and adult kidney tumors. Using single cell mRNA reference maps of normal tissues, we quantify reference “cellular signals” in each tumor. Quantifying global differentiation, we find that childhood tumors exhibit fetal cellular signals, replacing the presumption of “fetalness” with a quantitative measure of immaturity. By contrast, in adult cancers our assessment refutes the suggestion of dedifferentiation towards a fetal state in most cases. We find an intimate connection between developmental mesenchymal populations and childhood renal tumors. We demonstrate the diagnostic potential of our approach with a case study of a cryptic renal tumor. Our findings provide a cellular definition of human renal tumors through an approach that is broadly applicable to human cancer.
Author(s): Young MD, Mitchell TJ, Custers L, Margaritis T, Morales-Rodriguez F, Kwakwa K, Khabirova E, Kildisiute G, Oliver TRW, de Krijger RR, van den Heuvel-Eibrink MM, Comitani F, Piapi A, Bugallo-Blanco E, Thevanesan C, Burke C, Prigmore E, Ambridge K, Roberts K, Braga FAV, Coorens THH, Del Valle I, Wilbrey-Clark A, Mamanova L, Stewart GD, Gnanapragasam VJ, Rampling D, Sebire N, Coleman N, Hook L, Warren A, Haniffa M, Kool M, Pfister SM, Achermann JC, He X, Barker RA, Shlien A, Bayraktar OA, Teichmann SA, Holstege FC, Meyer KB, Drost J, Straathof K, Behjati S
Publication type: Article
Publication status: Published
Journal: Nature Communications
Year: 2021
Volume: 12
Issue: 1
Print publication date: 01/12/2021
Online publication date: 23/06/2021
Acceptance date: 25/05/2021
ISSN (electronic): 2041-1723
Publisher: Nature Research
URL: https://doi.org/10.1038/s41467-021-23949-5
DOI: 10.1038/s41467-021-23949-5
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