BETHESDA, MD USA (UroToday.com) - Dr. W. Kimryn Rathmell gave a short presentation about the role of SETD2 mutations in clear cell renal cell carcinoma (ccRCC).
ccRCC is well-known to harbor mutations on chromosome 3p that in most cases result in loss of VHL/HIF pathway and increased hypoxia signaling and metabolic changes. However, work over the last 4 years has shown that at least 3 other 3p genes are targeted by somatic mutation. 
These include PBRM1, BAP1, and SETD2. Although the function of these genes is still being elucidated, they all are known to modify chromatin. SETD2 is a histone lysine methltransferase which methylates histone H3 on lysine 36. This modification exerts its effect by altering chromatin density. She provided an entertaining metaphor with UNC basketball coach “tight” and “loose” Roy Williams and compacted and de-condensed chomatin. Chromatin density may play a role in gene expression and gene splicing, as changes in chromatin accessibility occurred within actively transcribed genes in a clinical model. Interestingly, the mutation was also associated with changes in RNA splicing in up to 25% of expressed genes.
She hopes that further functional studies may reveal therapy targets in ccRCC.
Presented by:
W. Kimryn Rathmell, MD, PhD
University of North Carolina Lineberger Comprehensive Cancer Center
Reported by:
Philip Abbosh, MD, PhD from the 2014 Winter Meeting of the Society of Urologic Oncology (SUO) "Defining Excellence in Urologic Oncology" - December 3 - 5, 2014 - Bethesda, MD USA
*Fox Chase Cancer Center, Philadelphia, PA USA