Tet2-Loss Modifies Androgen Signaling In Prostate Cancer

Molecular markers for metastatic prostate cancer (PCa) can be identified by sequencing metastatic tumor genomes. We recently identified cancer gene mutations in a patient with metastatic disease using next generation sequencing (NGS) of DNA from 5 metastatic tumors and blood. We characterized a somatic non-conservative substitution in the methylcytosine dioxygenase ten-eleven translocation 2 (TET2) in all metastatic tumors but not the blood or primary adenocarcinoma. Analysis of metastatic tumors from additional patients revealed frequent somatic loss and sequence alteration of TET2, which was previously observed to be altered in 5-15% of myeloid, kidney and colon cancer. Genome-wide association studies previously identified non-coding risk variants associated with PCa and melanoma, and rare germline missense variants are observed in African-Americans with PCa. We sought to further investigate …