Research Papers:

Copy number variations in urine cell free DNA as biomarkers in advanced prostate cancer

Yun Xia, Chiang-Ching Huang, Rachel Dittmar, Meijun Du, Yuan Wang, Hongyan Liu, Niraj Shenoy, Liang Wang, Manish Kohli _

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Oncotarget. 2016; 7:35818-35831. https://doi.org/10.18632/oncotarget.9027

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Yun Xia1,2, Chiang-Ching Huang3, Rachel Dittmar2, Meijun Du2, Yuan Wang2, Hongyan Liu2, Niraj Shenoy4, Liang Wang2 and Manish Kohli4

1 Department of General Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

2 Department of Pathology and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA

3 Joseph J. Zilber School of Public Health, University of Wisconsin, Milwaukee, WI, USA

4 Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, MN, USA

Correspondence to:

Manish Kohli, email:

Keywords: prostate cancer, liquid biopsy, urine, cell free DNA, next generation sequencing

Received: December 08, 2015 Accepted: April 16, 2016 Published: April 26, 2016


Genetic profiling of urine cell free DNA (cfDNA) has not been evaluated in advanced prostate cancer. We performed whole genome sequencing of urine cfDNAs to identify tumor-associated copy number variations in urine before and after initiating androgen deprivation therapy in HSPC stage and docetaxel chemotherapy in CRPC stage. A log2 ratio-based copy number analysis detected common genomic abnormalities in prostate cancer including AR amplification in 5/10 CRPC patients. Other abnormalities identified included TMPRSS2-ERG fusion, PTEN gene deletion, NOTCH1 locus amplification along with genomic amplifications at 8q24.3, 9q34.3, 11p15.5 and 14q11.2, and deletions at 4q35.2, 5q31.3, 7q36.3, 12q24.33, and 16p11.2. By comparing copy number between pre- and post-treatment, we found significant copy number changes in 34 genomic loci. To estimate the somatic tumor DNA fraction in urine cfDNAs, we developed a Urine Genomic Abnormality (UGA) score algorithm that summed the top ten most significant segments with copy number changes. The UGA scores correlated with tumor burden and the change in UGA score after stage-specific therapies reflected disease progression status and overall survival. The study demonstrates the potential clinical utility of urine cfDNAs in predicting treatment response and monitoring disease progression.

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