ASCO 2017: BRCA1/2 reversion mutations in prostate cancer identified from clinical tissue and liquid biopsy samples
Of the 2284 patients, 236 (11.2%) had ≥1 deleterious BRCA GA. This is consistent with prior studies of BRCA mutation incidence in advance prostate cancer.1 Of these, 10 samples harbored potential revGA in BRCA1 (1) or BRCA2 (9); by histology, the patients had prostate acinar adenocarcinoma (7), neuroendocrine carcinoma (1), or undifferentiated carcinoma (2). Of these, 2 were identified from liquid biopsies (blood), 5 from FFPE tissue samples (liver), 1 from prostate, 1 from a lymph node, and 1 sample was from a bone marrow core biopsy. All ten were from patients with metastases. The incidence of BRCA mutations and BRCA reversions were similar in prostate cancer as in breast cancer, ovarian cancer, and hepatobiliary cohorts.
When looking at specific mutation types in prostate cancer BRCA genes compared to those other three malignancies, indels (small insertions or deletions) were more common (70% vs. 36-41%), and deletions and splice mutations were not present (0% vs. 7-23%).
This study, which is the first of its kind, demonstrates the feasibility of NGS to identify revGA from both liquid and solid biopsies. Additionally, its presence was associated with metastatic disease. It may be associated with PARP inhibitor resistance or even platinum-based chemotherapy resistance. Further studies are warranted, despite its relative rarity in this population.
Presented By: Sugganth Daniel, MD, Foundation Medicine, Inc., Cambridge, MA
Co-Author(s): Erica Gornstein, Garrett Michael Frampton, James Sun, Samantha Morley, Andreas Heilmann, Prasanth Reddy, Jon Chung, James Suh, Shakti Ramkissoon, Eric Allan Severson, Jo-Anne Vergilio, Philip J. Stephens, Vincent A. Miller, Julia Andrea Elvin, Jeffrey S. Ross, Laurie M. Gay
Institution(s): Foundation Medicine, Inc., Morrisville, NC; Foundation Medicine, Inc., Cambridge, MA; Albany Medical College, Albany, NY
Written By: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto
Twitter: @tchandra_uromd
at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 - Chicago, Illinois, USA
REFERENCES:
1. Mateo J, Boysen G, Barbieri CE, Bryant HE, Castro E, Nelson PS, Olmos D, Pritchard CC, Rubin MA, de Bono JS. DNA Repair in Prostate Cancer: Biology and Clinical Implications. Eur Urol. 2017 Mar;71(3):417-425. doi: 10.1016/j.eururo.2016.08.037. Epub 2016 Aug 31. Review.