Alterations in BRAF have been reported in 3-5% of prostate cancer, although further characterization is lacking. Here, we describe the nature of BRAF alterations in prostate cancer using a large cohort from commercially available tissue and liquid biopsies subjected to comprehensive genomic profiling (CGP).
Tissue and liquid biopsies from patients with prostate cancer were profiled using FoundationOne®CDx and FoundationOne®Liquid CDx CGP assays, respectively. Tissue biopsies from non-prostate cancer types were used for comparison (n=275,151). Genetic ancestry was predicted using a single nucleotide polymorphism-based approach.
Among 15,864 tissue biopsies, BRAF-activating alterations were detected in 520 cases (3.3%). The majority (463 samples, 2.9%) harbored Class II alterations, including BRAF rearrangements (243 samples, 1.5%), K601E (101 samples, 0.6%), and G469A (58 samples, 0.4%). BRAF-altered prostate cancers were enriched for CDK12 mutations (OR 1.87, 9.2% vs 5.2%, p=0.018), but depleted in TMPRSS2 fusions (OR 0.25, 11% vs 32%, p<0.0001), PTEN alterations (OR 0.47, 17% vs 31%, p<0.0001), and APC alterations (OR 0.48, 4.4% vs 8.9%, p=0.018) relative to BRAF wild-type disease. Compared to patients of European ancestry, BRAF alterations were more common in tumors from patients of African ancestry (5.1% vs. 2.9%, p<0.0001) and Asian ancestry (6.0% vs. 2.9%, p<0.001).
Activating BRAF alterations were detected in ~3% of prostate cancers, and most were Class II mutations and rearrangements; BRAF V600 mutations were exceedingly rare. These findings suggest that BRAF activation in prostate cancer is unique from other cancers and supports further clinical investigation of therapeutics targeting the MAPK pathway.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2023 Jul 21 [Epub ahead of print]
Alex Chehrazi-Raffle, Hanna Tukachinsky, Eamon Toye, Smruthy Sivakumar, Alexa B Schrock, Hannah E Bergom, Hedyeh Ebrahimi, Sumanta Pal, Tanya Dorff, Neeraj Agarwal, Brandon A Mahal, Geoffrey R Oxnard, Justin Hwang, Emmanuel S Antonarakis
City Of Hope National Medical Center, Duarte, CA, United States., Foundation Medicine Inc., Cambridge, MA, United States., University of Minnesota, Minneapolis, Minnesota, United States., Foundation Medicine, Cambridge, MA, United States., University of Minnesota, Minneapolis, United States., University of Utah/Huntsman Cancer Institute, Salt lake City, UT, United States., University of Miami, United States., Foundation Medicine, Cambridge, United States., University of Minnesota, Minnesota, MN, United States.