Abstract 2733: Comparison of copy number aberrations (CNAs) between plasma cell free DNA (cfDNA) and tissue DNA in metastatic castrate resistant prostate cancer (mCRPC)

2017 ◽  
Author(s):  
Chiang-Ching Huang ◽  
Meijun Du ◽  
Liguo Wang ◽  
Yen-chen Lin ◽  
Hua Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Plasma Cell ◽  
Copy Number ◽  
Cell Free Dna ◽  
Copy Number Aberrations ◽  
Free Dna ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

Association of plasma cell-free DNA concentration [cfDNA] with outcome from taxane therapy (TT) for castration resistant prostate cancer (CRPC).

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 5014-5014 ◽  
Author(s):  
Niven Mehra ◽  
Rossitza Christova ◽  
Lorna Pope ◽  
Suzanne Carreira ◽  
Jane Goodall ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Plasma Cell ◽  
Castration Resistant Prostate Cancer ◽  
Cell Free Dna ◽  
Dna Concentration ◽  
Castration Resistant ◽  
Free Dna

Plasma cell free DNA (cfDNA) based somatic aberrations detected in treatment naïve metastatic hormone sensitive prostate cancer (mHSPC), hormonally ablated mHSPC and metastatic castration resistant prostate cancer (mCRPC) states and their impact on survival.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5047-5047
Author(s):  
Manish Kohli ◽  
Winston Tan ◽  
Tiantian Zheng ◽  
Amy Wang ◽  
Calvin Wong ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Plasma Cell ◽  
Copy Number Variations ◽  
Cell Free Dna ◽  
Androgen Ablation ◽  
Free Dna ◽  
Impact On Survival ◽  
Treatment Naïve ◽  
The Impact ◽  
Somatic Aberrations

5047 Background: We identified plasma cell free DNA (cfDNA) based copy number variations (CNV); single nucleotide variants (SNVs) & TMPRSS-ERG fusion in four sub states of metastatic prostate cancer (mPCa) and determined the impact on survival. Two mHSPC cohorts included treatment naïve, gp-1 and mHSPC patients (pts) responding to chronic androgen ablation (AA) (gp-2). Two mCRPC cohorts included mHSPC pts with PSA relapse on chronic AA (gp-3) and a clinically progressive mCRPC cohort post AA (gp-4). Methods: Enrollment of mPCa pts was performed from 2009-14 who were followed until 2018. Plasma from collected blood was used for extracting cfDNA. NGS was performed using Illumina HiSeq X for a preselected target panel of 129 genes including DNA damage repair genes. Statistical analyses of genomic aberrations were performed in R 3.5.1 and Cox proportional-hazard models were used for survival analyses. Results: A total of 255 pts were enrolled with 215 having adequate cfDNA that passed NGS QC. Median study follow up was 90.2 (Range:73;99) months. The table highlights pts in each gp with CNV, SNV, fusion events. ARamplification was higher in mCRPC gps3&4 (20/103 pts) compared to 3/106 pts in mHSPC gps1&2 (p < 0.001) and was prognostic for poor survival in mCRPC (p < 0.001;HR:3.34; 95%CI: 1.9-5.76). 54/103 pts in gp3&4 had SNVs in TP53 compared to 34/106 pts in mHSPC gps1&2 (P < 0.01). SNVs in APC, AR, CDK12 and BRIP1 were also increased in gps3&4 (p < 0.01). Gp1 mHSPC pts with SNVs in ATM/ CHEK2 had shorter response to AA (p < 0.001; HR:3.66; 95%: CI:1.81-7.39). Conclusions: Plasma cfDNA based somatic aberrations are detected with increased prevalence in mHSPC to mCRPC states. The ease of specimen collection and the need for molecular profiling in mPCa increases its potential for clinical applications in pt care. [Table: see text]

Cell-free DNA (cfDNA) analysis and evaluation of BRAF amplifications and mutations in metastatic castration-resistant prostate cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 255-255
Author(s):  
Peter Steinwald ◽  
Elisa Ledet ◽  
Bryce Raymon Christensen ◽  
Marcus Marie Moses ◽  
Lynne Chapman ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Analysis ◽  
Castration Resistant Prostate Cancer ◽  
Braf Mutations ◽  
Cell Free Dna ◽  
Variants Of Unknown Significance ◽  
Free Dna ◽  
Increased Risk ◽  
Unknown Significance ◽  
Castrate Resistant

255 Background: Cell-free DNA (cfDNA) is an accessible method for characterizing tumoral alterations. We report cfDNA screenings of prostate cancer pts positive for BRAF amplifications/mutations in pts with metastatic CRPC. Methods: Guardant360 testing (Guardant Health, Inc.) assesses cell-free DNA analysis using sequencing to identify genomic alterations in 73 cancer-related genes in circulation. A total of 133 metastatic castrate resistant prostate cancer (mCRPC) pts in various stages of therapy had Guardant cfDNA analyses. Treatment histories prior to testing and concurrent cfDNA alterations were analyzed. Results: BRAF amplifications were detected in 32 (24%) mCRPC pts; 5 pts had concurrent BRAF mutations. Of the mutations detected, only one (K601E, n = 2) was a known activating mutation while all others were variants of unknown significance (VUS). One K601E mutation pt had no other cfDNA alterations. Additionally, 4 pts without BRAF amplification had VUS BRAF mutations. BRAF amplification pts had ≥ 2 concurrent gene amplifications/alterations with the median being 8. The most common recurrent amplifications/alterations were AR (75%), p53 (59%), CDK6 (53%), MET (50%), and MYC (50%). Abiraterone (Abi) and/or Enzalutamide (Enza) resistance was associated with BRAF amplification (p = 0.0042). Non-Abi/Enza resistance pts were less likely to have BRAF amplification. The 2 pts with BRAF K601E mutation were treated with targeted protocol therapy without success however one K601E pts was subsequently treated with cabazitaxel+carboplatin which produced a positive clinical response and a 99.79% reduction in PSA. Conclusions: Pts resistant to Abi/Enza have an increased risk of developing BRAF amplifications. BRAF amplifications arise in the context of multiple additional detectable cfDNA alterations. Identification of actionable mutations, such as BRAF K601E, illustrates the potential for cfDNA testing to direct pt treatment. As cfDNA profiling continues to expand, the ability translate alterations into clinically actionable strategies is critical.

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