Review Genetics and epigenetics of renal cell cancer Marcella M.L. Baldewijns a , Iris J.H. van Vlodrop a , Leo J. Schouten b , Patricia M.M.B. Soetekouw c , Adriaan P. de Bruïne a , Manon van Engeland a, ⁎ a Department of Pathology, GROW — School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands b Department of Epidemiology, GROW — School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands c Division of Medical Oncology, Department of Internal Medicine, University Hospital Maastricht, Maastricht, The Netherlands Received 2 August 2007; received in revised form 4 December 2007; accepted 9 December 2007 Available online 15 December 2007 Abstract Renal cell carcinoma (RCC) is not a single disease, but comprises a group of tumors of renal epithelial origin, each with a different histology, displaying a different clinical course and caused by different genetic alterations. Since cure rates are inversely associated with stage and response to the available treatment regimes is limited to a subgroup of patients, diagnostic methods facilitating early detection and new therapeutic modalities are necessary. Increased knowledge of the underlying pathophysiology of RCC has resulted in the identification of genetic alterations involved in renal cell cancer carcinogenesis. Promising agents to target these pathways, especially the angiogenesis pathway, are being developed, some of which are already standard of care. In addition to genetics, knowledge on epigenetics in the process of renal tumorigenesis has been significantly increased in the last decades. Epigenetics will play an increasing role in the development of new therapeutic modalities and may deliver new prognostic and early diagnostic markers. In this review we discuss the background of RCC and the clinical applications of RCC genetics and epigenetics. © 2007 Elsevier B.V. All rights reserved. Keywords: Renal cell carcinoma; Kidney cancer; Genetics; Epigenetics; DNA methylation Contents 1. Introduction ............................................................. 134 1.1. Descriptive epidemiology ................................................... 134 1.2. Risk factors .......................................................... 134 1.3. Classification ......................................................... 135 1.4. Prognosis ........................................................... 137 1.5. Therapy ............................................................ 138 1.5.1. Local therapy ..................................................... 138 1.5.2. Systemic therapy ................................................... 138 2. Genetics of RCC ........................................................... 138 2.1. Clear cell renal cell carcinoma — von Hippel-Lindau (VHL) tumor suppressor gene .................... 138 2.2. Papillary renal cell carcinoma — MET proto-oncogene .................................... 139 2.3. Papillary renal cell carcinoma — fumarate hydratase (FH) tumor suppressor gene ...................... 140 2.4. Chromophobe renal cell carcinoma — Birt-Hogg-Dubé (BHD) tumor suppressor gene ................... 140 2.5. Renal cell carcinoma in tuberous sclerosis — tuberous sclerosis complex 1 (TSC1) and 2 (TSC2) tumor suppressor genes ... 140 2.6. Clinical applications ..................................................... 141 Available online at www.sciencedirect.com Biochimica et Biophysica Acta 1785 (2008) 133 – 155 www.elsevier.com/locate/bbacan ⁎ Corresponding author. Department of Pathology, GROW — School for Oncology and Developmental Biology, University Maastricht, P.O. Box 616, 6200 MD Maastricht, The Netherlands. Tel.: +31 433874622; fax: +31 433876613. E-mail address: m.vanengeland@path.unimaas.nl (M. van Engeland). 0304-419X/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.bbcan.2007.12.002