scholarly journals Epigenetic Analysis of Circulating Tumor DNA in Localized and Metastatic Prostate Cancer: Evaluation of Clinical Biomarker Potential

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1362
Author(s):  
Marianne Trier Bjerre ◽  
Maibritt Nørgaard ◽  
Ole Halfdan Larsen ◽  
Sarah Østrup Jensen ◽  
Siri H. Strand ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
De Novo ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Healthy Controls ◽  
Tissue Samples ◽  
Castration Resistant ◽  
Clinical Biomarker ◽  
Epigenetic Analysis ◽  
Tumor Dna

Novel and minimally-invasive prostate cancer (PCa)-specific biomarkers are needed to improve diagnosis and risk stratification. Here, we investigated the biomarker potential in localized and de novo metastatic PCa (mPCa) of methylated circulating tumor DNA (ctDNA) in plasma. Using the Marmal-aid database and in-house datasets, we identified three top candidates specifically hypermethylated in PCa tissue: DOCK2, HAPLN3, and FBXO30 (specificity/sensitivity: 80%–100%/75–94%). These candidates were further analyzed in plasma samples from 36 healthy controls, 61 benign prostatic hyperplasia (BPH), 102 localized PCa, and 65 de novo mPCa patients using methylation-specific droplet digital PCR. Methylated ctDNA for DOCK2/HAPLN3/FBXO30 was generally not detected in healthy controls, BPH patients, nor in patients with localized PCa despite a positive signal in 98%–100% of matched radical prostatectomy tissue samples. However, ctDNA methylation of DOCK2, HAPLN3, and/or FBXO30 was detected in 61.5% (40/65) of de novo mPCa patients and markedly increased in high- compared to low-volume mPCa (89.3% (25/28) vs. 32.1% (10/31), p < 0.001). Moreover, detection of methylated ctDNA was associated with significantly shorter time to progression to metastatic castration resistant PCa, independent of tumor-volume. These results indicate that methylated ctDNA (DOCK2/HAPLN3/FBXO30) may be potentially useful for identification of hormone-naïve mPCa patients who could benefit from intensified treatment.

Circulating tumor DNA-targeted sequencing to reveal germline and somatic alterations that can guide decision-making in metastatic castration-resistant prostate cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17556-e17556
Author(s):  
Baijun Dong ◽  
Liancheng Fan ◽  
Bin Yang ◽  
Wei Chen ◽  
Yonghong Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Circulating Tumor Dna ◽  
Targeted Sequencing ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Genomic Landscape ◽  
Platinum Based Chemotherapy ◽  
Somatic Alterations ◽  
Multiple Treatments ◽  
Tumor Dna

e17556 Background: The genomic landscape of metastatic castration-resistant prostate cancer (mCRPC) is dynamic with the application of multiple treatments. The circulating tumor DNA (ctDNA), which reveals germline and somatic alterations, provides a mini-invasive tool for monitoring tumor evolution. Methods: We performed an exploratory analysis of 299 ctDNA samples from 8 centers through application of multiple-gene deep targeted sequencing. Results: The most common recurrent genomic alterations were in AR(34.7%), TP53(18.9%), CDK12(15.4%), BRCA2(13.3%), and the majority of these clinically actionable gene alterations were identified in somatic level (CDK12 100% in somatic). The results showed the frequency of AR amplification and TP53 defect significantly increased in post-second and later line treatment group compared with treatment-naive group. AR amplification and TP53 or RB1 defect were associated with resistance to abiraterone or docetaxel. CDK12 was more frequently altered in our cohort than those in previous reports which mainly focused on Caucasian population. The patients with CDK12 defect showed rapid resistance to abiraterone and limited efficacy of Poly (ADP-ribose) polymerase inhibitors (PARPi). However, these patients seemed to benefit from chemotherapy, especially platinum-based chemotherapy. Conclusions: This multi-institutional real-world study explored the genomic landscape and captured the significant diversity of mCRPC at different treatment stages by liquid biopsy. These findings established genomic drivers associated with resistance to multiple treatments (including PARPi and platinum-based chemotherapy) in mCRPC. Hence, ctDNA targeted sequencing can help guide clinical decision making in mCRPC throughout the whole treatment process. CDK12 might be able to be a novel predictive biomarker to guide treatment selection in mCRPC.

scholarly journals Circulating tumor DNA alterations in patients with metastatic castration‐resistant prostate cancer

Cancer ◽  
2019 ◽  
Vol 125 (9) ◽  
pp. 1459-1469 ◽  
Author(s):  
Guru Sonpavde ◽  
Neeraj Agarwal ◽  
Gregory Russell Pond ◽  
Rebecca J. Nagy ◽  
Roberto H. Nussenzveig ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Circulating Tumor Dna ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Dna Alterations ◽  
Tumor Dna

scholarly journals Circulating Tumor DNA Abundance and Potential Utility in De Novo Metastatic Prostate Cancer

2019 ◽  
Vol 75 (4) ◽  
pp. 667-675 ◽  
Author(s):  
Gillian Vandekerkhove ◽  
Werner J. Struss ◽  
Matti Annala ◽  
Heini M.L. Kallio ◽  
Daniel Khalaf ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
De Novo ◽  
Circulating Tumor Dna ◽  
Potential Utility ◽  
Tumor Dna

scholarly journals Liquid Biopsy from Bile-Circulating Tumor DNA in Patients with Biliary Tract Cancer

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4581
Author(s):  
Jin-Yi Han ◽  
Keun Soo Ahn ◽  
Tae-Seok Kim ◽  
Yong Hoon Kim ◽  
Kwang Bum Cho ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Liquid Biopsy ◽  
Survival Rates ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Strong Positive Correlation ◽  
Kras Mutations ◽  
Tissue Samples ◽  
Ffpe Samples ◽  
Tumor Dna

Although liquid biopsy of blood is useful for cancer diagnosis and prediction of prognosis, diagnostic and prognostic value of ctDNA in bile fluid for BTCs are not clear yet. To determine whether liquid biopsy for circulating tumor DNA (ctDNA) can replace tissue biopsy when assessing somatic mutations in biliary tract cancers (BTCs). Bile samples were obtained from 42 patients with BTC. Matched formalin-fixed paraffin-embedded (FFPE) samples were obtained from 20 of these patients and matched plasma samples from 16 of them. Droplet digital PCR (ddPCR) was used for detection KRAS somatic mutation. KRAS mutations were identified in the bile ctDNA of 20 of 42 (48%) patients. Patients with mutant KRAS showed significantly worse survival than those with wild-type KRAS (2-year survival rates: 0% vs. 55.5%, respectively; p = 0.018). There was 80.0% mutational concordance between the paired bile ctDNA and FFPE samples, and 42.9% between the plasma and FFPE samples. On transcriptomic sequencing of one set of paired bile and FFPE samples, expression level of KRAS-associated signaling oncogenes in the bile and tissue samples showed a strong positive correlation (r = 0.991, p < 0.001). Liquid biopsy of bile reliably detect mutational variants within the bile ctDNA of BTC patients. These results suggest that bile is an effective biopsy fluid for ctDNA analysis.

scholarly journals PD14-09 CIRCULATING TUMOR DNA PRIOR TO THERAPY INITIATION IN DE NOVO METASTATIC PROSTATE CANCER

2018 ◽  
Vol 199 (4S) ◽  
Author(s):  
Werner J Struss ◽  
Gillian Vandekerkhove ◽  
Matti Annala ◽  
Kevin Beja ◽  
Kim N Chi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
De Novo ◽  
Circulating Tumor Dna ◽  
Therapy Initiation ◽  
Tumor Dna
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