Charting the Genetic Landscape of Genitourinary Cancers

Recent large-scale sequencing efforts have been instrumental in delineating the most significantly mutated cancer genes across many common cancer types. Still, most of these efforts have primarily interrogated coding sequences, which constitute only a small fraction (<2%) of the genome.  Many alterations in noncoding or poorly mappable regions of the cancer genome may hence remain to be discovered.

Prostate Cancer: Using linked-read whole genome sequencing, we recently described highly-recurrent duplications involving a novel long-range enhancer of the androgen receptor (AR) in > 80% of cases of castration-resistant prostate cancer. These pervasive alterations play an important role in mediating resistance to anti-androgen therapies.

​MiT/TFE translocation renal cell carcinoma (tRCC): Our laboratory has a special interest in the genetics and biology of tRCC, a rare but highly aggressive subtype of kidney cancer without effective therapies. This cancer is driven by oncogenic gene fusions involving a transcription factor in the MiT/TFE family, usually TFE3 located on chromosome Xp11.2. Through a large-scale genomic effort, we have recently described the molecular and clinical landmarks of tRCC.