SETD2 and PBRM1 inactivation in the development of clear cell renal cell carcinoma

Kidney cancer of the clear cell type is often lethal and causes more than 100,000 deaths worldwide every year. Understanding the biology of this cancer type may help to develop better ways to diagnose and treat it. Damage in DNA (genes) is present in all cancer cells and clear cell kidney cancer is no exception. Exactly how these DNA changes contribute to the development of kidney cancer is still mostly unclear. The PhD study undertaken by Jun Li (Genetics department, UMCG) looked at the effects of damage in 2 genes that appear to be important in kidney cancer: SETD2 and PBRM1. Normal kidney cells cannot be grown in culture for many days, but after silencing the SETD2 gene the growth potential of these cells in became abnormally large. This suggests that damage to SETD2 can contribute to the change from normal kidney cells into cancer cells. In contrast, silencing the PBRM1 gene did not show this effect. However, it did cause changes in the activity of other genes, especially of some involved in immune response. These changes were, more strongly, also observed in kidney cancer cells. Together, these findings contribute to our further understanding of the biology of kidney cancer and may help in improving diagnostics and treatment of this aggressive cancer type.