Journal article

Germline Mutations in the CDKN2B Tumor Suppressor Gene Predispose to Renal Cell Carcinoma

Mariam Jafri, Naomi C Wake, David B Ascher, Douglas EV Pires, Dean Gentle, Mark R Morris, Eleanor Rattenberry, Michael A Simpson, Richard C Trembath, Astrid Weber, Emma R Woodward, Alan Donaldson, Tom L Blundell, Farida Latif, Eamonn R Maher



UNLABELLED: Familial renal cell carcinoma (RCC) is genetically heterogeneous and may be caused by mutations in multiple genes, including VHL, MET, SDHB, FH, FLCN, PTEN, and BAP1. However, most individuals with inherited RCC do not have a detectable germline mutation. To identify novel inherited RCC genes, we undertook exome resequencing studies in a familial RCC kindred and identified a CDKN2B nonsense mutation that segregated with familial RCC status. Targeted resequencing of CDKN2B in individuals (n = 82) with features of inherited RCC then revealed three candidate CDKN2B missense mutations (p.Pro40Thr, p.Ala23Glu, and p.Asp86Asn). In silico analysis of the three-dimensional structures ind..

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Funding Acknowledgements

M. Jafri is in receipt of a Medical Research Council Clinical Research Fellowship. D.B. Ascher is supported by a National Health and Medical Research Council CJ Martin Fellowship. D.E.V. Pires is supported by the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)-Brazil. M.A. Simpson thanks the National Institutes for Health Research (NIHR) Biomedical Research Centre based at Guy's and St. Thomas' NHS Foundation Trust and King's College London for financial support. E.R. Maher thanks the Association for International Cancer Research (AICR; now Worldwide Cancer Research), The Eveson Charitable Trust, and the NIHR Biomedical Research Centre based at Cambridge for financial support.