SAN FRANCISCO, CA USA (UroToday.com) - The Cancer Genome Atlas (TCGA) version of the clear cell renal cell (ccRCC) genome was published in June 2013, and Dr. Roeland Verhaak presented an update of the original iteration.
This is a landmark contribution and the original manuscript had almost 350 authors and analyzed 400+ tumors. The data currently has almost 500 tumors, though. Mutations in chromatin modifiers PBRM1, BAP1, and SETD2 predominate in addition to well-known VHL mutations. These mutations all cluster on chromosome 3p, and, in fact, loss of one copy of 3p was present in > 90% of tumors with an epigenetic modifier mutation. Additionally, mutations in the AKT/PTEN/PI3K pathway are also common. Copy number variations (CNV) include 5q amplifications, which probably target SQSTM1, and this amplification seems to be exclusive of mutations in AKT/PTEN/PI3K, suggesting that the (druggable) AKT axis might be a fruitful target for drug development.
Dr. Verhaak highlighted the fact that ccRCC seems to be a different type of animal because of the lack of mutations in common cancer genes and relative lack of CNVs. A relatively unexplored area is the ccRCC metabalome, which Dr. Verhaak alluded to.
Highlights of a presentation by Roeland Verhaak, PhD at the 2014 Genitourinary Cancers Symposium - January 30 - February 1, 2014 - San Francisco Marriott Marquis - San Francisco, California USA
MD Anderson Cancer Center, Houston, TX USA