Washington, DC (UroToday.com): In this session, Dr. Schultz commenced by discussing the history of genomics in prostate cancer. In 1996, androgen receptor mutations were first noted. This was followed in 2004 with the discovery of ETS fusions. In 2010, DNA-bopsy number change differences were reported and 2012 provided the discovery of SPOP and FOXA1 deletions. These studies included roughly 100 samples per study.
This year, two larger scale studies added volumes to our knowledge of genomics in prostate cancer. The TCGA study included 333 primary tumors and explored whole exome sequencing, DNA-copy number, RNA expression, and DNA methylation (The Cancer Genome Atlas Research Network, Cell 2015). Investigators were able to divided 74% of tumors into 7 distinct subtypes – ERG, ETV1, ETV4, FLI1, SPOP, FOXA1, IDH1 – all of which demonstrated marked heterogeneity, even within subgroups. Epigenetic changes also defined distinct subsets of prostate cancer. In particular, the IDH-1 mutant subgroup is the most hypermethylated in prostate cancer. These hypermethylations are also seen in other cancers (GBM and leukemia), but are more profound in prostate cancer and may be associated with early age of disease onset. Finally, several potentially actionable DNA repair defects were noted particularly in PI3K and ras signaling pathways.
The second report was from the PCF/SU2C group and looked at 150 metastatic tumors with regard to whole exome sequencing, DNA-copy number variation, and RNA expression (Robinson et al, Cell 2015). There were more copy number changes and mutations in metastatic disease relative to primary tumor group. In addition, AR pathway, PI3K signaling, and DNA repair were more often effected in metastatic disease.
In order to make these data more accessible to every day clinicians and patients without a computational oncology background, Dr. Schultz introduced the cBioPortal (http://cbioportal.org). The portal compiles all known genomic data for a variety of malignancies and can provide mutation locations and patterns allowing for a cross cancer comparison of mutations.
There is no doubt that we are on the cusp of more individualized therapies for patients with prostate cancer.
Nikolaus Schultz, MD.
Benjamin T. Ristau, MD. from the Society of Urologic Oncology Meeting - December 2 - 4, 2015 – Washington, DC.
Fox Chase Cancer Center, Temple University Health System, Philadelphia PA.