SAN FRANCISCO, CA USA (UroToday.com) - Dr. James Walter Mier presented 2 articles from the basic science literature in renal cancer from the past year.
The first article looked at the role of SQSTM1 in renal cell carcinoma (RCC) (Li L, et al. Cancer Cell (2013) 24: 738-50). Chromosome 5q amplification is a known genetic alteration in RCC though not much is known about how the genes at this site contribute to the disease. The study focused on the 5q35.3 locus and found that 12 genes were overexpressed, one of which was SQSTM1, which is a known oncogene in other settings. The group found that higher expression of SQSTM1 was associated with higher Fuhrman grade. They were able to show that knockdown of the gene reduced colony formation and tumor growth whereas overexpression of the gene resulted in the opposite. The group was able to show that SQSTM1 likely promotes tumor growth through activation of mTOR, which suggests that RCC patients with 5q amplification may benefit from therapies targeting mTOR.
The second study presented by Dr. Mier looked at genetic alterations leading to increased metastatic potential (Vanharanta S, et al. Nat Met (2013) 19:50-6). This group was able to create an RCC cell line which exhibits high metastatic potential, particularly to the lungs, which Dr. Mier pointed out has been difficult to accomplish in RCC research. Using this cell line, the group identified genes that were overexpressed in metastasis through array data. They focused on a subset of genes known to be upregulated by VHL loss of function, in particular CXCR4. They found that enhanced expression of CXCR4 is due entirely to epigenetic changes, with variations in histone methylation in the area of the CXCR4 attributed to changes in the levels of PRC2 components, in particular SUZ12.
Highlights of a presentation by James Walter Mier, MD at the 2014 Genitourinary Cancers Symposium - January 30 - February 1, 2014 - San Francisco Marriott Marquis - San Francisco, California USA
Dana-Farber Cancer Institute, Boston, MA USA