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Pathogenic BRAF Mutations in Prostate Cancer: Frequency and Distribution

ASCO Genitourinary Cancers Symposium 2023 PRESENTATION
Authors Elisa M. Ledet, Elizabeth Mauer, Calvin Y. Chao, A. Oliver Sartor

Background:Human cancers are known to harbor mutations in BRAF, a rare but clinically significant finding. BRAF p. V600E is the most common hot spot mutation and has been well described, however other activating mutations are less well studied. Herein we evaluate the landscape of BRAF pathogenic/likely pathogenic (P/LP) variations in prostate cancer patients.

Methods:De-identified records from patients with primary prostate cancer who underwent NGS with Tempus xF (ctDNA, 105 genes) or xT (tissue, DNAseq of 648 genes, 500× coverage, full transcriptome RNAseq for a subset of patients) were analyzed from a real-world dataset.

Results:There were 5,902 patients identified with prostate cancer who underwent any Tempus xT testing, of whom 85 (1.4%) harbored a P/LP BRAF mutation. Of these 85 patients, the most prevalent BRAF mutation identified was BRAF K601E (Lys601Glu) (36% of total), followed by Gly469Ala (18%) and Leu597Arg (8%, Table) There were 4,177 patients identified with primary prostate cancer who underwent any Tempus xF testing, of whom 50 (1.2%) harbored a P/LP BRAF mutation. Similarly, the most prevalent BRAF mutation identified was BRAF K601E (26%).

Conclusions:This study presents the first large-scale genomic characterization of BRAF mutations in patients with prostate cancer using both tissue and ctDNA NGS analysis. Among thousands of samples from prostate cancer patients, K601E was the most common BRAF mutation. This confirms findings of smaller studies and has implications for developmental therapeutics. Further studies should document the natural history of BRAF K601E in prostate cancer.

Most frequent P/LP BRAF mutations all tissue (xT) and ctDNA (xF) samples amongst patients with any identified BRAF P/LP mutation.
Tissue, N=5,902 ctDNA, N=4,177
BRAF Mutation N=85 BRAF Mutation N=50
Lys601Glu 31 (36%) Lys601Glu 13 (26%)
Gly469Ala 15 (18%) Val600Glu 10 (20%)
Leu597Arg 7 (8%) Gly469Ala 4 (8.0%)
Val600Glu 4 (4.7%) Asp594Asn 2 (4.0%)
Asp594Gly 3 (3.5%) Asp594Gly 2 (4.0%)