ASCO GU 2017: The long tail of significantly mutated genes in prostate cancer - Session Highlights
Both spatially (at different spots in the tumor) and temporally ( at different times along the treatment algorithm). However, there are several basic mutations which are common throughout the tumors and at different times. These mutations are well characterized. However, Larger cohorts allow for identification of additional mutations that may play a role in the pathogenesis of prostate cancer. Aggregation and uniform analysis of larger cohorts can reveal significantly mutated genes and pathways in the "long tail" (1-5% of cases).
In 918 prostate cancer specimens, mutational significance analysis defined 37 new gene mutations (e.g. SPEN, SETD2). These gene mutations are implicated in other tumors as well. Several pathways are involved in these gene mutations. For example, mutations in epigenetic regulators and chromatin remodelers are enriched in ETS-negative tumors. 14% show alterations in ubiquitin pathway such as CUL3, mutually exclusive with SPOP mutations. Enrichment of splicing pathway alterations, SPEN mutations were also identified. Finally primary and metastatic sites were compared. TP53,AR, PTEN , FOXA1, APC and BRCA2 alterations are enriched in metastatic samples while SPOP mutations and FOXP1/RYBP deletions are enriched in primary tumors.
Presented By: Joshua Armenia
Written By: Miki Haifler, MD, M.Sc, Fox Chase Cancer Center
at the 2017 Genitourinary Cancers Symposium - February 16 - 18, 2017 – Orlando, Florida USA