Plasma genetic and genomic abnormalities predict treatment response and clinical outcome in advanced prostate cancer
| Autor: | Raymond Hovey, William A. See, Liang Wang, Meijun Du, Michael Tschannen, Debashis Nandy, Xuexia Wang, Elizabeth A. Worthey, Deepak Kilari, Rachel L. Dittmar, Chiang Ching Huang, Howard J. Jacob, Yuan Wang, Tiezheng Yuan, Manish Kohli, Shu Xia, Adam M. Lee, Yongchen Guo |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Oncology PCA3 medicine.medical_specialty DNA Copy Number Variations Biopsy Recombinant Fusion Proteins Gene Dosage Genome-wide association study Bioinformatics Androgen deprivation therapy Plasma Prostate cancer Transcriptional Regulator ERG Prostate Internal medicine medicine Humans PTEN Copy-number variation Liquid biopsy Aged Gene Library next generation sequencing Aged 80 and over liquid biopsy cell free DNA Base Sequence biology Genome Human Serine Endopeptidases PTEN Phosphohydrolase Prostatic Neoplasms Androgen Antagonists DNA Neoplasm Sequence Analysis DNA Middle Aged prostate cancer medicine.disease Treatment Outcome medicine.anatomical_structure Trans-Activators biology.protein Research Paper Genome-Wide Association Study |
| Zdroj: | Scopus-Elsevier Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.3845 |
| Popis: | Liquid biopsies, examinations of tumor components in body fluids, have shown promise for predicting clinical outcomes. To evaluate tumor-associated genomic and genetic variations in plasma cell-free DNA (cfDNA) and their associations with treatment response and overall survival, we applied whole genome and targeted sequencing to examine the plasma cfDNAs derived from 20 patients with advanced prostate cancer. Sequencing-based genomic abnormality analysis revealed locus-specific gains or losses that were common in prostate cancer, such as 8q gains, AR amplifications, PTEN losses and TMPRSS2-ERG fusions. To estimate tumor burden in cfDNA, we 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 (p < 0.04). 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 these treatments. These 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. |
| Databáze: | OpenAIRE |
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