@article{10902/6219,
year = {2015},
month = {3},
url = {http://hdl.handle.net/10902/6219},
abstract = {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 ~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.},
publisher = {Nature Publishing Group},
publisher = {Nature Communications. 2015 Mar 19;6:6336},
title = {Recurrent chromosomal gains and heterogeneous driver mutations characterise papillary renal cancer evolution},
author = {Kovac, Michal and Navas, Carolina and Horswell, Stuart and Salm, Max and Bardella, Chiara and Rowan, Andrew and Stares, Mark and Castro Giner, Francesc and Fisher, Rosalie and Bruin, Elza C. de and Kovacova, Monika and Gorman, Maggie and Makino, Seiko and Williams, Jennet and Jaeger, Emma and Jones, Angela and Howarth, Kimberley and Larkin, James and Varela Egocheaga, Ignacio and Pickering, Lisa},
}