**1. Introduction**

Kidney and urinary tract cancers accounted for a total of 16936 cases and 6764 deaths in 2007 in Japan (Matsuda et al., 2012), which is roughly 2% of all cancers. Renal cell carcinoma (RCC) is the most common type of kidney cancer, and is classified into three major subtypes, clear cell RCC, papillary RCC and chromophobe RCC, representing 80, 10, and 5% of all RCCs, and the majority of renal tumors are sporadic although 2-4% are hereditary (Hagenkord et al., 2011).

A number of genes have been studied in association with renal tumors, including those involved in tumorigenesis, and the progression and outcome of the cancer, by means of mutational searches, gene expression profiling, proteomics/metabolomics and pathological/ clinical studies. The genes can be classified into several categories, such as familial, sporadic, epigenetic and quantitative, depending on the timing of their expression, and the factors affecting their effects, such as microRNA (miRNA) and metabolites have emerged. Since tumorigenesis is believed to be initiated with genetic/epigenetic modulations of at least several genes, but not a single gene alone, the balance among these cancer-related genes is considered to be more important than the contribution of a dramatic change caused by a single gene. Thus, an extensive and competitive search for oncogenes and tumor suppressor genes based on the search for their mutations was immediately accompanied by the search for interacting proteins/factors at the mutation sites. This indicates that lineages of gene functions, or signaling pathways, are important to understanding tumorigenesis, as well as the progression and outcome of the cancer. Although such pathways are not fully understood, it is important to summarize the latest knowledge of genes and their functions in terms of the coordinated functions of genes to achieve a basic understanding of cancer and to use the information obtained for diagnostics/therapeutics.

Here, we summarize and discuss the genes associated with renal tumors (Section 2) and then show one of them, *Kank1*, from gene-function networks or signaling pathways (Section 3). We

© 2013 Kiyama et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 Kiyama et al.; licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

also discuss a methodology for collecting information on multiple gene functions with a simple pathological system (Section 4).

kidney, pancreas and adrenal glands. The *VHL* gene encodes the 30-kDa protein VHL, 213 amino acid residues long, and is implicated in the regulation of hypoxia-inducible factors (HIFs) (Maher et al., 2011). The VHL protein forms a complex with elongin B, elongin C and cullin-2, and the complex has ubiquitin ligase E3 activity and is involved in the ubiquitination and degradation of HIFα, the α subunits of transcription factors HIF-1 and HIF-2, which form a dimer with HIFβ and regulate the transcription of hypoxia-inducible genes such as those for VEGF (vascular endothelial growth factor), PDGF (platelet derived growth factor) and TGFα (transforming growth factor α) (Kondo and Kaelin, 2001; Kaelin, 2009; Fig. 1). However, the cancer found in VHL disease is sporadic and the lifetime risk of RCC in VHL disease patients is about 70% (Maher et al., 2011). So, it is reasonable to assume that additional genes are involved in RCC and the mutations in *VHL* are not the definitive cause of RCC, which is one of the reasons to explore new genes and genetic loci (see below). Meanwhile, the status of the *VHL* gene is important for the treatment of VHL disease and kidney cancer patients. HIFresponsive gene products, such as VEGF and PDGF, activate the angiogenesis of tumors and therefore are good therapeutic targets. Inhibitors of VEGF and PDGF, sunitinib and sorafenib,

Genetics of Renal Tumors http://dx.doi.org/10.5772/54588 5

have been approved by the US Food and Drug Administration (Kaelin, 2009).

**Figure 1.** Summary of signal transduction pathways associated with RCC.
