Molecular Biology and Genetics

Renal cell carcinoma (RCC) is a heterogeneous disease that includes several histologically distinct subtypes. The molecular genetic defects that occur in sporadic adult renal cell carcinoma are extensive and complex, ranging from single DNA mutations to large chromosomal defects. This overview will focus on the molecular genetic defects that are present within the renal cell tumors rather than the histological stratification of the different subtypes. Some of the existing evidence that a defined genetic mutation contributes to tumor development will be presented. While this view likely represents an oversimplified model of renal tumor development, it is based on the notion that genetic changes strongly associated with a tumor type confer a selective advantage for those cells in the cell population. In addition to the abnormalities described in this chapter, individual renal tumors contain between 5 and 70 somatic mutations in the coding exons of additional genes. It is, therefore, important to consider that many of the common mutations discussed in the subsequent pages occur in the background of several additional cellular defects.