SAN FRANCISCO, CA USA (UroToday.com) - Several recently published iterations of the clear cell renal cell carcinoma (ccRCC) genome have demonstrated recurrent mutations in BAP1 and PBRM1. Dr. James Brugarolas presented data regarding the role of these two genes.
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The overarching goal of his work is to come up with additional ways to classify ccRCC by developing biomarkers that are based on these recurrent mutations, which is rational if tumor biology is determined by these mutations. He presented the case for classifying tumors containing BAP1 mutations as a novel subclass of ccRCC. BAP1-mutant tumors tend to be high grade and have a lower overall survival in separate cohorts. This finding prompted his lab to develop a BAP1 immunohistochemical analysis which performs very well in detecting BAP1 loss in a large cohort of tumors, assessed on a tumor microarray. The relationship between BAP1 and patient outcome was again demonstrated in a third large cohort of patients. BAP1 staining also adds information to prognostic nomograms like UCLA and SSIGN. Although the creation of a new subclassification ccRCC would be a step in the right direction, this subclassification will not translate into improving patient outcomes until the biology of BAP1 is better understood and drugs that target that pathway can be developed. Dr. Brugarolas presented convincing data for further molecular biological evaluation of this novel target.
Highlights of a presentation by James Brugarolas, MD, PhD at the 2014 Genitourinary Cancers Symposium - January 30 - February 1, 2014 - San Francisco Marriott Marquis - San Francisco, California USA
The University of Texas Southwestern Medical Center, Dallas, TX USA