Plasma Genetic and Genomic Abnormalities Predict Treatment Response and Clinical Outcome in Advanced Prostate Cancer

Shu Xia, from the Huazhong University of Science and Technology and the Medical College of Wisconsin, and others recently published their research in Oncotarget. Their research evaluated tumor-associated genomic and genetic variations in plasma cell-free DNA (cfDNA) and their associations with treatment response and overall patient survival.

Drs. Xia and others used the NEXTflex DNA Sequencing Kit and NEXTflex DNA Barcodes to construct libraries from cell free DNA obtained from 20 patients with advanced prostate cancer for whole genome and targeted sequencing. Samples were taken from each patient both before treatment for prostate cancer and after treatment began.

Their analysis revealed locus-specific gains or losses that were common in prostate cancer. To estimate tumor burden in cfDNA, they developed a Plasma Genomic Abnormality (PGA) score by summing the most significant copy number variations. Cox regression analysis showed that PGA scores were significantly associated with overall survival. After androgen deprivation therapy or chemotherapy, targeted sequencing showed significant mutational profile changes in genes involved in androgen biosynthesis, AR activation, DNA repair and chemotherapy resistance. 

These changes may reflect the dynamic evolution of heterozygous tumor populations in response to the treatments. Additionally, their results strongly support the feasibility of using non-invasive liquid biopsies as potential tools to study biological mechanisms underlying therapy-specific resistance and to predict disease progression in advanced prostate cancer.

Xia, S., et al. (2015) Plasma genetic and genomic abnormalities predict treatment response and clinical outcome in advanced prostate cancer. Oncotarget, 5.

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