Using joint genomic-transcriptomic analysis of 243 samples, we reveal recurrent patterns of nongenetic evolution in ccRCC not exclusively governed by genetic factors, including T-cell depletion, tumor T-cell receptor coevolution, potential cGAS-STING repression, and increased cell proliferation. These patterns can aid clinical management and guide novel treatment approaches.
Cancer discovery. 2025 Jan 09 [Epub ahead of print]
Ángel Fernández-Sanromán, Annika Fendler, Benjy J Y Tan, Anne-Laure Cattin, Charlotte Spencer, Rachael Thompson, Lewis Au, Irene Lobon, Husayn Ahmed Pallikonda, Alice Martin, Fiona Byrne, Antonia Franz, Anna Mikolajczak, Haseeb Rahman, Zayd Tippu, Scott T C Shepherd, Hugang Feng, Daqi Deng, Andrew Rowan, Lisa Pickering, Andrew J S Furness, Kate Young, David Nicol, Sarah Maria Rudman, Tim O'Brien, Kim Edmonds, Ashish Chandra, Steve Hazell, Kevin Litchfield, George Kassiotis, James Larkin, Samra Turajlic
Cancer Dynamics Laboratory, The Francis Crick Institute, London, United Kingdom., Department of Urology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Berlin, Germany., Retroviral Immunology, The Francis Crick Institute, London, United Kingdom., Experimental Histopathology Unit, The Francis Crick Institute, London, United Kingdom., Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London, United Kingdom., Department of Urology, the Royal Marsden NHS Foundation Trust, London, United Kingdom., Skin and Renal Unit, Royal Marsden NHS Foundation Trust, London, United Kingdom., Department of Oncology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom., Urology Centre, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom., Cellular Pathology Department, St Thomas' Hospital, London, United Kingdom., Department of Pathology, the Royal Marsden NHS Foundation Trust, London, United Kingdom., Tumour Immunogenomics and Immunosurveillance (TIGI) Lab, UCL Cancer Institute, London, United Kingdom.