TY - JOUR AU - Young, Matthew D AU - Mitchell, Thomas J AU - Custers, Lars AU - Margaritis, Thanasis AU - Morales-Rodriguez, Francisco AU - Kwakwa, Kwasi AU - Khabirova, Eleonora AU - Kildisiute, Gerda AU - Oliver, Thomas R W AU - de Krijger, Ronald R AU - van den Heuvel-Eibrink, Marry M AU - Comitani, Federico AU - Piapi, Alice AU - Bugallo-Blanco, Eva AU - Thevanesan, Christine AU - Burke, Christina AU - Prigmore, Elena AU - Ambridge, Kirsty AU - Roberts, Kenny AU - Braga, Felipe A Vieira AU - Coorens, Tim H H AU - Del Valle, Ignacio AU - Wilbrey-Clark, Anna AU - Mamanova, Lira AU - Stewart, Grant D AU - Gnanapragasam, Vincent J AU - Rampling, Dyanne AU - Sebire, Neil AU - Coleman, Nicholas AU - Hook, Liz AU - Warren, Anne AU - Haniffa, Muzlifah AU - Kool, Marcel AU - Pfister, Stefan M AU - Achermann, John C AU - He, Xiaoling AU - Barker, Roger A AU - Shlien, Adam AU - Bayraktar, Omer A AU - Teichmann, Sarah A AU - Holstege, Frank C AU - Meyer, Kerstin B AU - Drost, Jarno AU - Straathof, Karin AU - Behjati, Sam TI - Single cell derived mRNA signals across human kidney tumors. JO - Nature Communications VL - 12 IS - 1 SN - 2041-1723 CY - [London] PB - Nature Publishing Group UK M1 - DKFZ-2021-01433 SP - 3896 PY - 2021 AB - 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. LB - PUB:(DE-HGF)16 C6 - pmid:34162837 DO - DOI:10.1038/s41467-021-23949-5 UR - https://inrepo02.dkfz.de/record/169353 ER -