The Experts below are selected from a list of 5130 Experts worldwide ranked by ideXlab platform
Yaoqing Shen - One of the best experts on this subject based on the ideXlab platform.
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whole genome sequencing in metastatic breast cancer lessons learned from the bc cancer personalized Oncogenomics program
Journal of Clinical Oncology, 2018Co-Authors: Nathalie Levasseur, Yaoqing Shen, Karen A. Gelmon, Eric Y. Zhao, Janessa Laskin, Marco A Marra, S ChiaAbstract:12065Background: The emerging interest in precision medicine has lead to the genomic profiling of breast cancer, with the intent of identifying therapeutically targetable alterations. The clinical ...
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Personalized oncogenomic analysis of metastatic adenoid cystic carcinoma: using whole-genome sequencing to inform clinical decision-making.
Cold Spring Harbor molecular case studies, 2018Co-Authors: Manik Chahal, Yaoqing Shen, Erin Pleasance, Karen Mungall, Jasleen K. Grewal, Eric Y. Zhao, Tony Ng, Erin Chapman, Martin R. Jones, Melika BonakdarAbstract:Metastatic adenoid cystic carcinomas (ACCs) can cause significant morbidity and mortality. Because of their slow growth and relative rarity, there is limited evidence for systemic therapy regimens. Recently, molecular profiling studies have begun to reveal the genetic landscape of these poorly understood cancers, and new treatment possibilities are beginning to emerge. The objective is to use whole-genome and transcriptome sequencing and analysis to better understand the genetic alterations underlying the pathology of metastatic and rare ACCs and determine potentially actionable therapeutic targets. We report five cases of metastatic ACC, not originating in the salivary glands, in patients enrolled in the Personalized Oncogenomics (POG) Program at the BC Cancer Agency. Genomic workup included whole-genome and transcriptome sequencing, detailed analysis of tumor alterations, and integration with existing knowledge of drug-target combinations to identify potential therapeutic targets. Analysis reveals low mutational burden in these five ACC cases, and mutation signatures that are commonly observed in multiple cancer types. Notably, the only recurrent structural aberration identified was the well-described MYB-NFIB fusion that was present in four of five cases, and one case exhibited a closely related MYBL1-NFIB fusion. Recurrent mutations were also identified in BAP1 and BCOR, with additional mutations in individual samples affecting NOTCH1 and the epigenetic regulators ARID2, SMARCA2, and SMARCB1. Copy changes were rare, and they included amplification of MYC and homozygous loss of CDKN2A in individual samples. Genomic analysis revealed therapeutic targets in all five cases and served to inform a therapeutic choice in three of the cases to date.
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Whole genome and transcriptome sequencing of lung cancer: Options for personalized cancer treatment.
Journal of Clinical Oncology, 2017Co-Authors: Negar Chooback, Cheryl Ho, Yaoqing Shen, Erica S. Tsang, Yongjun Zhao, Andrew J. Mungall, Richard A. Moore, Daniel John Renouf, Karen A. GelmonAbstract:e20567Background: Targeted therapy against driver mutations has revolutionized lung cancer management. The Personalized Oncogenomics (POG) program uses whole genome and transcriptome derived inform...
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Clinical outcomes after whole genome sequencing in patients with metastatic non-small cell lung cancer.
Journal of Clinical Oncology, 2017Co-Authors: Erica S. Tsang, Negar Chooback, Cheryl Ho, Yaoqing Shen, Daniel John Renouf, Martin Jones, Erin PleasanceAbstract:e20563Background: The Personalized Oncogenomics (POG) program at the BC Cancer Agency integrates whole genome (DNA) and RNA sequencing into practice for metastatic malignancies. We examine patients...
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personalized Oncogenomics in the management of gastrointestinal carcinomas early experiences from a pilot study
Current Oncology, 2016Co-Authors: Brandon S Sheffield, Yaoqing Shen, Daniel John Renouf, Erin Pleasance, Katayoon Kasaian, Steven J M Jones, Basile Tessiercloutier, H Lichang, Yisu Li, David G HuntsmanAbstract:Background Gastrointestinal carcinomas are genomically complex cancers that are lethal in the metastatic setting. Whole-genome and transcriptome sequencing allow for the simultaneous characterization of multiple oncogenic pathways. Methods We report 3 cases of metastatic gastrointestinal carcinoma in patients enrolled in the Personalized Onco-Genomics program at the BC Cancer Agency. Real-time genomic profiling was combined with clinical expertise to diagnose a carcinoma of unknown primary, to explore treatment response to bevacizumab in a colorectal cancer, and to characterize an appendiceal adenocarcinoma. Results In the first case, genomic profiling revealed an IDH1 somatic mutation, supporting the diagnosis of cholangiocarcinoma in a malignancy of unknown origin, and further guided therapy by identifying epidermal growth factor receptor amplification. In the second case, a BRAF V600E mutation and wild-type KRAS profile justified the use of targeted therapies to treat a colonic adenocarcinoma. The third case was an appendiceal adenocarcinoma defined by a p53 inactivation; Ras/raf/mek, Akt/mtor, Wnt, and notch pathway activation; and overexpression of ret, erbb2 (her2), erbb3, met, and cell cycle regulators. Summary We show that whole-genome and transcriptome sequencing can be achieved within clinically effective timelines, yielding clinically useful and actionable information.
Rosy Mondal - One of the best experts on this subject based on the ideXlab platform.
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application and optimization of minimally invasive cell free dna techniques in Oncogenomics
Tumor Biology, 2018Co-Authors: Manish Kumar, Yashmin Choudhury, Sankar Kumar Ghosh, Rosy MondalAbstract:The conventional method of measuring biomarkers in malignant tissue samples has already given subversive growth in cancer diagnosis, prognosis, and therapy selection. However, the regression and heterogeneity associated with tumor tissue biopsy have urged for the development of an alternative approach. Considering the limitations, cell-free DNA has emerged as a surrogate alternative, facilitating preoperative chemoradiotherapy (p < 0.0001) treatment response in rectal cancer and detection of biomarker in lung cancer. This potential of cell-free DNA in several other cancers has yet to be explored based on clinical relevance by optimizing the preanalytical factors. This review has highlighted the crucial parameters from blood collection to cell-free DNA analysis that has a significant impact on the accuracy and reliability of clinical data. The quantity of cell-free DNA is also a limiting factor. Therefore, a proper preanalytical factor for blood collection, its stability, centrifugation speed, and plasma s...
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Application and optimization of minimally invasive cell-free DNA techniques in Oncogenomics:
Tumor Biology, 2018Co-Authors: Manish Kumar, Yashmin Choudhury, Sankar Kumar Ghosh, Rosy MondalAbstract:The conventional method of measuring biomarkers in malignant tissue samples has already given subversive growth in cancer diagnosis, prognosis, and therapy selection. However, the regression and heterogeneity associated with tumor tissue biopsy have urged for the development of an alternative approach. Considering the limitations, cell-free DNA has emerged as a surrogate alternative, facilitating preoperative chemoradiotherapy (p
I C Baianu - One of the best experts on this subject based on the ideXlab platform.
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A Critical Evaluation of Clinical Trials in Cancer and Pharmacogenomics
Nature Precedings, 2012Co-Authors: I C BaianuAbstract:A critical overview of recent clinical trials in cancer is presented focused on signaling pathways blockers or inhibitors with a view to developing successful clinical trials employing personalized cancer therapies. Rational, pharmacogenomic strategies in cancer trials should be adopted that include specific molecular targeting based on adequate data for, and detailed modeling of, cancer cell genomes, modifications of cancer signaling pathways and epigenetic mechanisms. Novel translational Oncogenomics research is rapidly expanding through the application of highly sensitive and specific advanced technology, research findings and computational tools and complex models to both pharmaceutical and clinical problems. Multiple sample analyses from several recent clinical studies have shown that gene expression data for cancer cells can be employed to distinguish between tumor types as well as to predict outcomes. Potentially important applications of such results are individualized human cancer therapies or, in general, ‘personalized medicine’ that will have to be validated through optimally designed clinical trials in cancer. A Human Cancer Genomes and Epigenetics Project is proposed that can provide the essential data required for the optimal design of clinical trials with the goal of achieving significant improvements of the survival rates of cancer patients participating in clinical trials for advanced cancer stages. The results of such a six-year Human Cancer Genomes and Epigenetics Project should also greatly aid with the accelerated, rational development of effective anti-cancer medicines and the chemoprevention of cancers.
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Cancer Clinical Trials Optimization and Pharmacogenomics
Nature Precedings, 2012Co-Authors: I C BaianuAbstract:A critical overview of recent clinical trials in cancer is presented focused on signaling pathways blockers or inhibitors with a view to developing successful clinical trials employing personalized cancer therapies. Rational, pharmacogenomic strategies in cancer trials should be adopted that include specific molecular targeting based on adequate data for, and detailed modeling of, cancer cell genomes, modifications of cancer signaling pathways and epigenetic mechanisms. Novel translational Oncogenomics research is rapidly expanding through the application of highly sensitive and specific advanced technology, research findings and computational tools and complex models to both pharmaceutical and clinical problems. Multiple sample analyses from several recent clinical studies have shown that gene expression data for cancer cells can be employed to distinguish between tumor types as well as to predict outcomes. Potentially important applications of such results are individualized human cancer therapies or, in general,'personalized medicine' that will have to be validated through optimally designed clinical trials in cancer. A Human Cancer Genomes and Epigenetics Project is proposed that can provide the essential data required for the optimal design of clinical trials with the goal of achieving significant improvements of the survival rates of cancer patients participating in clinical trials for advanced cancer stages. The results of such a six-year Human Cancer Genomes and Epigenetics Project should also greatly aid with the accelerated, rational development of effective anti-cancer medicines and the chemoprevention of cancers.
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translational Oncogenomics and human cancer interactome networks recent developments complex system dynamic approaches and novel techniques
2012Co-Authors: I C BaianuAbstract:An overview of translational, human Oncogenomics, transcriptomics and cancer interactomic networks is presented together with basic concepts and potential, new applications to Oncology and Integrative Cancer Biology. Novel translational Oncogenomics research is rapidly expanding through the application of advanced technology, research findings and computational tools/models to both pharmaceutical and clinical problems. A self-contained presentation is adopted that covers both fundamental concepts and the most recent biomedical, as well as clinical, applications. Sample analyses in recent clinical studies have shown that gene expression data can be employed to distinguish between tumor types as well as to predict outcomes. Potentially important applications of such results are individualized human cancer therapies or, in general, ‘personalized medicine’. Several cancer detection techniques are currently under development both in the direction of improved detection sensitivity and increased time resolution of cellular events, with the limits of single molecule detection and picosecond time resolution already reached. The urgency for the complete mapping of a human cancer interactome with the help of such novel, high-efficiency / low-cost and ultra-sensitive techniques is also pointed out. Translational Oncogenomics and Integrative Cancer Biology in clinical applications and individualized cancer therapy/Pharmacogenomics; cancer clinical trials with signal pathways inhibitors; highsensitivity and high-speed microarray techniques (cDNA, oligonucleotide microarrays, protein arrays and tissue arrays) combined with novel dynamic NIR/fluorescence cross-correlation spectroscopy and dynamic microarray techniques; recent human cancer interactome network models of high-connectivity cancer proteins; global topology and Complex System Dynamics of the human cancer Interactome and differential gene expression (DGE) in human lung cancer; epigenomics in mammalian cells and development of new medicines for cancer therapy.
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translational Oncogenomics and human cancer interactomics advanced techniques and complex system dynamic approaches
2011Co-Authors: I C BaianuAbstract:An overview of translational, human Oncogenomics, transcriptomics and cancer interactomic networks is presented together with basic concepts and potential, new applications to Oncology and Integrative Cancer Biology. Novel translational Oncogenomics research is rapidly expanding through the application of advanced technology, research findings and computational tools/models to both pharmaceutical and clinical problems. A self-contained presentation is adopted that covers both fundamental concepts and the most recent biomedical, as well as clinical, applications. Sample analyses in recent clinical studies have shown that gene expression data can be employed to distinguish between tumor types as well as to predict outcomes. Potentially important applications of such results are individualized human cancer therapies or, in general, ‘personalized medicine’. Several cancer detection techniques are currently under development both in the direction of improved detection sensitivity and increased time resolution of cellular events, with the limits of single molecule detection and picosecond time resolution already reached. The urgency for the complete mapping of a human cancer interactome with the help of such novel, highefficiency, low-cost and ultra-sensitive techniques is also pointed out.
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Translational Oncogenomics and Human Cancer Interactome Networks:
Nature Precedings, 2011Co-Authors: I C BaianuAbstract:An overview of translational, human Oncogenomics, transcriptomics and cancer interactomic networks is presented together with basic concepts and potential, new applications to Oncology and Integrative Cancer Biology. Novel translational Oncogenomics research is rapidly expanding through the application of advanced technology, research findings and computational tools/models to both pharmaceutical and clinical problems. A self-contained presentation is adopted that covers both fundamental concepts and the most recent biomedical, as well as clinical, applications. Sample analyses in recent clinical studies have shown that gene expression data can be employed to distinguish between tumor types as well as to predict outcomes. Potentially important applications of such results are individualized human cancer therapies or, in general, ‘personalized medicine’. Several cancer detection techniques are currently under development both in the direction of improved detection sensitivity and increased time resolution of cellular events, with the limits of single molecule detection and picosecond time resolution already reached. The urgency for the complete mapping of a human cancer interactome with the help of such novel, high-efficiency / low-cost and ultra-sensitive techniques is also pointed out.
Sankar Kumar Ghosh - One of the best experts on this subject based on the ideXlab platform.
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application and optimization of minimally invasive cell free dna techniques in Oncogenomics
Tumor Biology, 2018Co-Authors: Manish Kumar, Yashmin Choudhury, Sankar Kumar Ghosh, Rosy MondalAbstract:The conventional method of measuring biomarkers in malignant tissue samples has already given subversive growth in cancer diagnosis, prognosis, and therapy selection. However, the regression and heterogeneity associated with tumor tissue biopsy have urged for the development of an alternative approach. Considering the limitations, cell-free DNA has emerged as a surrogate alternative, facilitating preoperative chemoradiotherapy (p < 0.0001) treatment response in rectal cancer and detection of biomarker in lung cancer. This potential of cell-free DNA in several other cancers has yet to be explored based on clinical relevance by optimizing the preanalytical factors. This review has highlighted the crucial parameters from blood collection to cell-free DNA analysis that has a significant impact on the accuracy and reliability of clinical data. The quantity of cell-free DNA is also a limiting factor. Therefore, a proper preanalytical factor for blood collection, its stability, centrifugation speed, and plasma s...
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Application and optimization of minimally invasive cell-free DNA techniques in Oncogenomics:
Tumor Biology, 2018Co-Authors: Manish Kumar, Yashmin Choudhury, Sankar Kumar Ghosh, Rosy MondalAbstract:The conventional method of measuring biomarkers in malignant tissue samples has already given subversive growth in cancer diagnosis, prognosis, and therapy selection. However, the regression and heterogeneity associated with tumor tissue biopsy have urged for the development of an alternative approach. Considering the limitations, cell-free DNA has emerged as a surrogate alternative, facilitating preoperative chemoradiotherapy (p
Erin Pleasance - One of the best experts on this subject based on the ideXlab platform.
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Personalized oncogenomic analysis of metastatic adenoid cystic carcinoma: using whole-genome sequencing to inform clinical decision-making.
Cold Spring Harbor molecular case studies, 2018Co-Authors: Manik Chahal, Yaoqing Shen, Erin Pleasance, Karen Mungall, Jasleen K. Grewal, Eric Y. Zhao, Tony Ng, Erin Chapman, Martin R. Jones, Melika BonakdarAbstract:Metastatic adenoid cystic carcinomas (ACCs) can cause significant morbidity and mortality. Because of their slow growth and relative rarity, there is limited evidence for systemic therapy regimens. Recently, molecular profiling studies have begun to reveal the genetic landscape of these poorly understood cancers, and new treatment possibilities are beginning to emerge. The objective is to use whole-genome and transcriptome sequencing and analysis to better understand the genetic alterations underlying the pathology of metastatic and rare ACCs and determine potentially actionable therapeutic targets. We report five cases of metastatic ACC, not originating in the salivary glands, in patients enrolled in the Personalized Oncogenomics (POG) Program at the BC Cancer Agency. Genomic workup included whole-genome and transcriptome sequencing, detailed analysis of tumor alterations, and integration with existing knowledge of drug-target combinations to identify potential therapeutic targets. Analysis reveals low mutational burden in these five ACC cases, and mutation signatures that are commonly observed in multiple cancer types. Notably, the only recurrent structural aberration identified was the well-described MYB-NFIB fusion that was present in four of five cases, and one case exhibited a closely related MYBL1-NFIB fusion. Recurrent mutations were also identified in BAP1 and BCOR, with additional mutations in individual samples affecting NOTCH1 and the epigenetic regulators ARID2, SMARCA2, and SMARCB1. Copy changes were rare, and they included amplification of MYC and homozygous loss of CDKN2A in individual samples. Genomic analysis revealed therapeutic targets in all five cases and served to inform a therapeutic choice in three of the cases to date.
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Clinical outcomes after whole genome sequencing in patients with metastatic non-small cell lung cancer.
Journal of Clinical Oncology, 2017Co-Authors: Erica S. Tsang, Negar Chooback, Cheryl Ho, Yaoqing Shen, Daniel John Renouf, Martin Jones, Erin PleasanceAbstract:e20563Background: The Personalized Oncogenomics (POG) program at the BC Cancer Agency integrates whole genome (DNA) and RNA sequencing into practice for metastatic malignancies. We examine patients...
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personalized Oncogenomics in the management of gastrointestinal carcinomas early experiences from a pilot study
Current Oncology, 2016Co-Authors: Brandon S Sheffield, Yaoqing Shen, Daniel John Renouf, Erin Pleasance, Katayoon Kasaian, Steven J M Jones, Basile Tessiercloutier, H Lichang, Yisu Li, David G HuntsmanAbstract:Background Gastrointestinal carcinomas are genomically complex cancers that are lethal in the metastatic setting. Whole-genome and transcriptome sequencing allow for the simultaneous characterization of multiple oncogenic pathways. Methods We report 3 cases of metastatic gastrointestinal carcinoma in patients enrolled in the Personalized Onco-Genomics program at the BC Cancer Agency. Real-time genomic profiling was combined with clinical expertise to diagnose a carcinoma of unknown primary, to explore treatment response to bevacizumab in a colorectal cancer, and to characterize an appendiceal adenocarcinoma. Results In the first case, genomic profiling revealed an IDH1 somatic mutation, supporting the diagnosis of cholangiocarcinoma in a malignancy of unknown origin, and further guided therapy by identifying epidermal growth factor receptor amplification. In the second case, a BRAF V600E mutation and wild-type KRAS profile justified the use of targeted therapies to treat a colonic adenocarcinoma. The third case was an appendiceal adenocarcinoma defined by a p53 inactivation; Ras/raf/mek, Akt/mtor, Wnt, and notch pathway activation; and overexpression of ret, erbb2 (her2), erbb3, met, and cell cycle regulators. Summary We show that whole-genome and transcriptome sequencing can be achieved within clinically effective timelines, yielding clinically useful and actionable information.
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Response to angiotensin blockade with irbesartan in a patient with metastatic colorectal cancer.
Annals of Oncology, 2016Co-Authors: M.r. Jones, Yaoqing Shen, Daniel John Renouf, Erin Pleasance, Kasmintan A. Schrader, Jacquie Schein, Andrew J. MungallAbstract:Background A patient suffering from metastatic colorectal cancer, treatment-related toxicity and resistance to standard chemotherapy and radiation was assessed as part of a personalized Oncogenomics initiative to derive potential alternative therapeutic strategies.
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abstract 1122 personalized Oncogenomics in advanced stage breast cancer
Cancer Research, 2015Co-Authors: Karen A. Gelmon, Yaoqing Shen, Martin Jones, Erin Pleasance, Katayoon Kasaian, S Chia, Caroline Lohrisch, Tamara Shenkier, Diego Villa, Peter EirewAbstract:Background Breast cancer is a complex disease with clinical, pathological, and molecular heterogeneity. Recent studies have identified several subtypes of breast cancers driven by specific molecular pathways that can be inhibited by targeted drugs. We studied the feasibility of using molecular data from whole genome and transcriptome sequencing of breast cancers to guide treatment. Methods Patients were consented as part of the Personalized Onco-Genomics (POG) study at the British Columbia Cancer Agency. Fresh tumor, blood for normal DNA, and archival tumor were collected. Tissue and blood samples were sequenced using the Ion Torrent AmpliSeq panel, followed by comprehensive DNA and RNA sequencing. In-depth bioinformatic analyses were performed. Somatic mutations, copy number changes, structural variants and gene expression were characterized. Results from genomic analyses were reviewed in a multi-disciplinary team. Results From August 2012 to October 2014, tissue samples from 30 patients with advanced stage breast cancer were analyzed. The median age at diagnosis was 53 years (range 32-75). The median number of lines of cytotoxic therapy prior to sequencing was 2 (range 0-10). All cases were invasive ductal carcinoma; 63% were ER+ and HER2-; 27% triple negative; 7% ER+ and HER2+; and 3% ER- and HER2+. The most frequently mutated genes were TP53 (67%), PI3KCA (23%), ESR1 (20%), ATM (10%), ARID1A (10%), and BRCA1/2 (10%). Somatic mutations in other genes of interest including HER2, PARP1, NF1, BAP1, PTEN, NOTCH1, were also identified. Molecular data were informative for patient care and/or actionable to guide treatment in 57% (17/30) of cases. Conclusion The use of whole genome sequencing technology to identify valuable molecular information to guide personalized breast cancer treatment is feasible. Further studies are warranted to evaluate the usefulness of genome-wide sequencing of breast cancers in clinical practice. Citation Format: Sophie Sun, Karen A. Gelmon, Stephen Chia, Caroline Lohrisch, Tamara Shenkier, Diego Villa, Yaoqing Shen, Martin Jones, Erin Pleasance, Katayoon Kasaian, Peter Eirew, Sreeja Leelakumari, Yusanne Ma, Tony Ng, Stephen Yip, Steven JM Jones, Marco A. Marra, Janessa J. Laskin. Personalized Oncogenomics in advanced stage breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1122. doi:10.1158/1538-7445.AM2015-1122
