期刊
NATURE COMMUNICATIONS
卷 6, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/ncomms7336
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资金
- Cancer Research UK [CR-UK A/16459]
- U-Care
- Genomic Medicine Theme of the Oxford NIHR Comprehensive Biomedical Research Centre
- Spanish Ministerio de Economia y Competitividad
- National Institute for Health Research University College London Hospitals Biomedical Research Centre
- Krebsliga beider Basel [11-2011]
- Krebsliga Zentralschweiz
- Wellcome Trust Centre for Human Genetics from the Wellcome Trust [090532/Z/09/Z]
- European Union Framework 7 PREDICT, RESPONSIFY
- European Research Council (THESEUS) grants
- Breast Cancer Research Foundation
- Prostate Cancer Research Foundation
- Rosetrees Trust
- EU ERC EVOCAN award
- RMH/ICR NIHR Biomedical Research Centre for Cancer
- Academy of Medical Sciences (AMS) [AMS-SGCL2-Tran] Funding Source: researchfish
- Cancer Research UK [19310, 17786] Funding Source: researchfish
- Rosetrees Trust [M179] Funding Source: researchfish
- The Francis Crick Institute [10174, 10170, 10359, 10172, 10002, 10001, 10303, 10169] Funding Source: researchfish
Papillary renal cell carcinoma (pRCC) is an important subtype of kidney cancer with a problematic pathological classification and highly variable clinical behaviour. Here we sequence the genomes or exomes of 31 pRCCs, and in four tumours, multi-region sequencing is undertaken. We identify BAP1, SETD2, ARID2 and Nrf2 pathway genes (KEAP1, NHE2L2 and CUL3) as probable drivers, together with at least eight other possible drivers. However, only similar to 10% of tumours harbour detectable pathogenic changes in any one driver gene, and where present, the mutations are often predicted to be present within cancer sub-clones. We specifically detect parallel evolution of multiple SETD2 mutations within different sub-regions of the same tumour. By contrast, large copy number gains of chromosomes 7, 12, 16 and 17 are usually early, monoclonal changes in pRCC evolution. The predominance of large copy number variants as the major drivers for pRCC highlights an unusual mode of tumorigenesis that may challenge precision medicine approaches.
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