The nuclear receptor coactivator NCOA2 was identified as a highly significant target gene on the 8q13 amplicon and is also subject to mutation in some tumors lacking gene amplification. Copy number gains or mutations in NCOA2 and other regulators of nuclear receptor function such as NCOA2 are present in primary tumors, thereby extending the potential importance of AR pathway perturbation to disease initiation. The frequency of NCOA2 alteration could be as high as 20 and 63 percent in primary and metastatic tumors respectively. The genomic and functional data suggest that NCOA2 functions as a driver oncogene in primary tumors by increasing AR signaling, which is known to play a critical role in early and late stage prostate cancer. This may be a potentially targettable pathway alteration in some settings.