Plasma genetic and genomic abnormalities predict treatment response and clinical outcome in advanced prostate cancer
| العنوان: | Plasma genetic and genomic abnormalities predict treatment response and clinical outcome in advanced prostate cancer |
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| المؤلفون: | 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 |
| المصدر: | Scopus-Elsevier Oncotarget |
| بيانات النشر: | Impact Journals, LLC, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| تدمد: | 1949-2553 |
| DOI: | 10.18632/oncotarget.3845 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ed1909a9dccbe2ad0086e6788a6e51ae https://doi.org/10.18632/oncotarget.3845 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ed1909a9dccbe2ad0086e6788a6e51ae |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19492553 |
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| DOI: | 10.18632/oncotarget.3845 |