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1دورية أكاديمية
المؤلفون: Jiang, Runze, Lu, Yi-Tsung, Ho, Hao, Li, Bo, Chen, Jie-Fu, Lin, Millicent, Li, Fuqiang, Wu, Kui, Wu, Hanjie, Lichterman, Jake, Wan, Haolei, Lu, Chia-Lun, OuYang, William, Ni, Ming, Wang, Linlin, Li, Guibo, Lee, Tom, Zhang, Xiuqing, Yang, Jonathan, Rettig, Matthew, Chung, Leland WK, Yang, Huanming, Li, Ker-Chau, Hou, Yong, Tseng, Hsian-Rong, Hou, Shuang, Xu, Xun, Wang, Jun, Posadas, Edwin M
المصدر: Oncotarget. 6(42)
مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Cancer, Genetics, Biotechnology, Urologic Diseases, Clinical Research, Human Genome, Prostate Cancer, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Base Sequence, Biomarkers, Tumor, Biopsy, Cell Separation, Chromosomes, Human, DNA Mutational Analysis, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Gene Rearrangement, Genetic Predisposition to Disease, Genome-Wide Association Study, Genomics, Humans, Laser Capture Microdissection, Liver Neoplasms, Male, Molecular Sequence Data, Mutation, Nanotechnology, Neoplastic Cells, Circulating, Oligonucleotide Array Sequence Analysis, Phenotype, Polymorphism, Single Nucleotide, Predictive Value of Tests, Prostatic Neoplasms, Time Factors, circulating tumor cell, prostate cancer, whole genome sequencing, liquid biopsy, cancer heterogeneity, Oncology and carcinogenesis
الوصف: Previous studies have demonstrated focal but limited molecular similarities between circulating tumor cells (CTCs) and biopsies using isolated genetic assays. We hypothesized that molecular similarity between CTCs and tissue exists at the single cell level when characterized by whole genome sequencing (WGS). By combining the NanoVelcro CTC Chip with laser capture microdissection (LCM), we developed a platform for single-CTC WGS. We performed this procedure on CTCs and tissue samples from a patient with advanced prostate cancer who had serial biopsies over the course of his clinical history. We achieved 30X depth and ≥ 95% coverage. Twenty-nine percent of the somatic single nucleotide variations (SSNVs) identified were founder mutations that were also identified in CTCs. In addition, 86% of the clonal mutations identified in CTCs could be traced back to either the primary or metastatic tumors. In this patient, we identified structural variations (SVs) including an intrachromosomal rearrangement in chr3 and an interchromosomal rearrangement between chr13 and chr15. These rearrangements were shared between tumor tissues and CTCs. At the same time, highly heterogeneous short structural variants were discovered in PTEN, RB1, and BRCA2 in all tumor and CTC samples. Using high-quality WGS on single-CTCs, we identified the shared genomic alterations between CTCs and tumor tissues. This approach yielded insight into the heterogeneity of the mutational landscape of SSNVs and SVs. It may be possible to use this approach to study heterogeneity and characterize the biological evolution of a cancer during the course of its natural history.
وصف الملف: application/pdf
الوصول الحر: https://escholarship.org/uc/item/9vx810dqTest
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2دورية أكاديمية
المؤلفون: Jiang, Runze, Lu, Yi-Tsung, Ho, Hao, Li, Bo, Chen, Jie-Fu, Lin, Millicent, Li, Fuqiang, Wu, Kui, Wu, Hanjie, Lichterman, Jake, Wan, Haolei, Lu, Chia-Lun, OuYang, William, Ni, Ming, Wang, Linlin, Li, Guibo, Lee, Tom, Zhang, Xiuqing, Yang, Jonathan, Rettig, Matthew, Chung, Leland WK, Yang, Huanming, Li, Ker-Chau, Hou, Yong, Tseng, Hsian-Rong, Hou, Shuang, Xu, Xun, Wang, Jun, Posadas, Edwin M
المصدر: Oncotarget. 6(42)
مصطلحات موضوعية: Chromosomes, Human, Humans, Liver Neoplasms, Prostatic Neoplasms, Genetic Predisposition to Disease, Biopsy, Oligonucleotide Array Sequence Analysis, Cell Separation, Predictive Value of Tests, Gene Expression Profiling, DNA Mutational Analysis, Genomics, Gene Expression Regulation, Neoplastic, Gene Rearrangement, Base Sequence, Phenotype, Mutation, Polymorphism, Single Nucleotide, Nanotechnology, Time Factors, Molecular Sequence Data, Male, Neoplastic Cells, Circulating, Genome-Wide Association Study, Laser Capture Microdissection, Biomarkers, Tumor, cancer heterogeneity, circulating tumor cell, liquid biopsy, prostate cancer, whole genome sequencing, Biomarkers, Tumor, Chromosomes, Human, Gene Expression Regulation, Neoplastic, Neoplastic Cells, Circulating, Polymorphism, Single Nucleotide, Oncology and Carcinogenesis
الوصف: Previous studies have demonstrated focal but limited molecular similarities between circulating tumor cells (CTCs) and biopsies using isolated genetic assays. We hypothesized that molecular similarity between CTCs and tissue exists at the single cell level when characterized by whole genome sequencing (WGS). By combining the NanoVelcro CTC Chip with laser capture microdissection (LCM), we developed a platform for single-CTC WGS. We performed this procedure on CTCs and tissue samples from a patient with advanced prostate cancer who had serial biopsies over the course of his clinical history. We achieved 30X depth and ≥ 95% coverage. Twenty-nine percent of the somatic single nucleotide variations (SSNVs) identified were founder mutations that were also identified in CTCs. In addition, 86% of the clonal mutations identified in CTCs could be traced back to either the primary or metastatic tumors. In this patient, we identified structural variations (SVs) including an intrachromosomal rearrangement in chr3 and an interchromosomal rearrangement between chr13 and chr15. These rearrangements were shared between tumor tissues and CTCs. At the same time, highly heterogeneous short structural variants were discovered in PTEN, RB1, and BRCA2 in all tumor and CTC samples. Using high-quality WGS on single-CTCs, we identified the shared genomic alterations between CTCs and tumor tissues. This approach yielded insight into the heterogeneity of the mutational landscape of SSNVs and SVs. It may be possible to use this approach to study heterogeneity and characterize the biological evolution of a cancer during the course of its natural history.
وصف الملف: application/pdf
الوصول الحر: https://escholarship.org/uc/item/9vx810dqTest