Contrasting Features of Papillary and Chromophobe Renal Cell Carcinoma Revealed by Whole-Genome Sequencing
The identification of cancer drivers is a cornerstone to delivery of precision oncology. So far sequencing of renal cell cancer (RCC) has largely been confined to the clear cell subtype of RCC. In contrast, sequencing analyses of the less common forms of RCC, papillary RCC (pRCC) and chromophobe RCC (ChRCC), have so far been limited. We analysed whole genome sequencing data on 164 tumour-normal pairs from the Genomics England 100,000 Genomes Project, providing a comprehensive, high-resolution map of copy number alterations, structural variation, and key global genomic features, including mutational signatures, intra-tumour heterogeneity and analysis of extrachromosomal DNA formation. Our research establishes correlations between genomic alterations and histological diversification and the extent to which genetically-mediated immune escape contributes to the development of these RCC subtypes. Implications: We demonstrate the distinctive genetics which characterises pRCC and ChRCC and how this information has the potential to inform patient treatment and clinical trials.
Authors
- Amit Sud (ORCID: https://orcid.org/0000-0002-6294-8222)
- Kevin Litchfield (ORCID: https://orcid.org/0000-0002-3725-0914)
- Andreas J Gruber (ORCID: https://orcid.org/0000-0001-7664-4257)
- Alex Cornish
- James R. Larkin (ORCID: https://orcid.org/0000-0002-4169-8447)
- Daniel Chubb
- Charlie Mills
- Samra Turajlic
- Lisa Browning
- Robert Bentham
- Richard S Houlston
- Richard Culliford
- Anna Frangou
- Samuel E D Lawrence
- Ben Kinnersley
- David C Wedge
Institutions
- Royal Marsden NHS Foundation Trust (GB)
- Institute of Cancer Research (GB)
- University of Konstanz (DE)
- The Francis Crick Institute (GB)
- Cancer Research UK (GB)
- London Cancer (GB)
- Cancer Research UK Manchester Institute (GB)
- Cancer Genetics (United States) (US)
- Oxford University Hospitals NHS Trust (GB)
- CRUK Lung Cancer Centre of Excellence (GB)
- Center for Systems Biology Dresden (DE)
- NIHR Manchester Biomedical Research Centre (GB)
- Max Planck Institute of Molecular Cell Biology and Genetics (DE)
- University College London (GB)
Publication Details
- Journal
- Molecular Cancer Research
- Published
- 2026-01-21
- DOI
- https://doi.org/10.1158/1541-7786.mcr-25-0616
- Primary Topic
- Renal cell carcinoma treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- U.S. Department of Defense
- Melanoma Research Alliance
- Wellcome Trust
- Francis Crick Institute
- Cancer Research UK
- National Institute for Health and Care Research
- Department of Health and Social Care
- Rosetrees Trust
- Medical Research Council