cancer genomics

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Cancer Genomics

Author : Graham Dellaire
ISBN : 9780123972743
Genre : Medical
File Size : 36. 28 MB
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Cancer Genomics addresses how recent technological advances in genomics are shaping how we diagnose and treat cancer. Built on the historical context of cancer genetics over the past 30 years, the book provides a snapshot of the current issues and state-of-the-art technologies used in cancer genomics. Subsequent chapters highlight how these approaches have informed our understanding of hereditary cancer syndromes and the diagnosis, treatment and outcome in a variety of adult and pediatric solid tumors and hematologic malignancies. The dramatic increase in cancer genomics research and ever-increasing availability of genomic testing are not without significant ethical issues, which are addressed in the context of the return of research results and the legal considerations underlying the commercialization of genomic discoveries. Finally, the book concludes with "Future Directions", examining the next great challenges to face the field of cancer genomics, namely the contribution of non-coding RNAs to disease pathogenesis and the interaction of the human genome with the environment. Tools such as sidebars, key concept summaries, a glossary, and acronym and abbreviation definitions make this book highly accessible to researchers from several fields associated with cancer genomics. Contributions from thought leaders provide valuable historical perspective to relate the advances in the field to current technologies and literature.

Cancer Genomics

Author : Michael Fraser
ISBN : 9780128061114
Genre : Medical
File Size : 89. 90 MB
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Prostate cancer (CaP) is the most commonly diagnosed malignancy in men in the Western world. In North America, more than 275000 men are diagnosed annually whereby approximately 1 in 6 men will be diagnosed with CaP in their lifetime, and 1 in 34 men will die from castrate-resistant metastatic disease. Unfortunately, current clinical prognostic factors explain only a proportion of the observed variation in clinical outcome from patient to patient. Furthermore, over-treatment of indolent and low-risk cancers leads to inappropriate morbidity following radiotherapy or surgery. As such, better predictors of individualized prognosis and treatment response are urgently needed to triage patients to customized and intensified CaP treatment. Recent developments in next-generation sequencing have made it possible to identify prognostic and predictive signatures based on genomic profiles. Herein, we review the recent genetic data pertaining to prostate cancer carcinogenesis, progression, castrate-resistance and metastases. We discuss the genetic basis of CaP progression from localized to systemic disease (e.g. point mutations, copy number alterations and structural variants) and important considerations for CaP biology including intra- and inter-prostatic heterogeneity, multifocality and multiclonality, TMPRSS2–ERG and other ETS-family gene fusions and the role of the tumor microenvironment (e.g. hypoxia and the contribution of caner-associated stroma). Finally, we focus on the use of genomic markers as prognostic factors for local failure and for systemic disease, as novel risk stratification tools, in triaging patients to existing treatment options and, ultimately, the potential of genomics for the identification of molecular targets for CaP therapy. We conclude by summarizing selected outstanding questions in CaP biology that can be addressed effectively through international cooperation between genome sequencing projects such as The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC).

Cancer Genomics

Author : Hye-Jung E. Chun
ISBN : 9780128060995
Genre : Medical
File Size : 57. 43 MB
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Cancer results from accumulated mutations in the genome. Sequencing is an accurate method to detect mutations. Second-generation sequencing technology, commonly referred to as next-generation sequencing technology, enables rapid, efficient and affordable DNA sequencing, and is transforming the scale and scope of cancer research. The technology is sufficiently flexible and affordable to allow sequencing of many cancer genomes, and thus facilitates both sequencing of samples from large patient cohorts and during disease progression in individual cancer patients. The high depths of redundant sequence coverage that can be obtained using some second-generation sequencing technologies, along with sequencing reads amplified from single DNA molecules, facilitate detection of subclones of cells in tumors. Large-scale genome sequencing of hundreds or even thousands of cancer samples is being conducted by several groups that aim to identify and characterize cancer driver mutations. Goals of such work, previously infeasible with Sanger sequencing instruments, are to use this information to improve cancer prognosis, diagnosis and therapeutic decision-making. The speed of data analysis is rate limiting, and investigators are struggling to accommodate and interpret the data deluge produced by second-generation technologies. In this chapter, we discuss cancer properties that are revealed by sequencing and the implication of such properties in experimental design and data interpretation. We describe past, current and upcoming sequencing technologies and the application of second-generation sequencing technologies in cancer genomics. Finally, we discuss the impact of second-generation sequencing technology in shaping personalized medicine.

Cancer Genomics

Author : Shile Zhang
ISBN : 9780128061015
Genre : Medical
File Size : 79. 70 MB
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The complexity of the transcriptome has been appreciated in recent years in light of the Encyclopedia of DNA Elements (ENCODE) project. While less than 3% of the genome is annotated with protein-coding genes, 62% of the genome is long RNA molecules (>200 nucleotides). With an increasing sequencing throughput and a decreasing cost, RNA sequencing (RNA-seq) is becoming a frequently used technology in transcriptome research. This chapter summarizes the advantages of RNA-seq compared to hybridization-based microarrays, the RNA-seq experiment workflow and reviews current applications of RNA-seq in the field of cancer research. With advantages in expression analysis of non-coding genes, fusion genes, investigation of expressed allelic imbalance, pseudogenes, viral integrated genes, and post-transcriptional regulation analysis including splicing, polyadenylation as well as RNA editing, RNA-seq technology has a tremendous potential to elucidate the complexity of the transcriptome and its working mechanisms in the initiation and development of cancer. Along with expression and pathway analysis, RNA-seq data can clarify the functional consequences of any potential genomic (DNA) variances and thus help to distinguish “driver” from “passenger” genomic events. In summary, RNA-seq allows a genome-wide interrogation of complex transcriptomes and will help elucidate important biological mechanisms linked to cancer phenotypes. In addition, the non-protein-coding transcriptome has the potential to provide novel biomarkers for early detection, diagnostics, prognostics and targets for therapy.

Cancer Genomics

Author : Matthew Parker
ISBN : 9780128061077
Genre : Medical
File Size : 62. 36 MB
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The vast amount of genomic data being produced by the research community is becoming readily accessible to biomedical researchers and clinicians to apply to their cancer(s) of interest. The major cancer genome projects, among others, The Cancer Genome Atlas (TCGA), the International Cancer Genome Consortium (ICGC) and the Pediatric Cancer Genome Project (PCGP) are contributing to this genomic data goldmine by sequencing hundreds to thousands of cancer genomes and supplementing these data with analyses such as gene expression and methylation. In addition to the raw data that are being made available through large data warehouses, “Data Portals” are becoming the norm for accessing and analyzing these data by third parties. We describe key features of some of these portals and other tools for the analysis of next-generation sequencing and other genomic data.

Cancer Genomics

Author : Ulrich Pfeffer
ISBN : 9789400758421
Genre : Medical
File Size : 38. 55 MB
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The combination of molecular biology, engineering and bioinformatics has revolutionized our understanding of cancer revealing a tight correlation of the molecular characteristics of the primary tumor in terms of gene expression, structural alterations of the genome, epigenetics and mutations with its propensity to metastasize and to respond to therapy. It is not just one or a few genes, it is the complex alteration of the genome that determines cancer development and progression. Future management of cancer patients will therefore rely on thorough molecular analyses of each single case. Through this book, students, researchers and oncologists will obtain a comprehensive picture of what the first ten years of cancer genomics have revealed. Experts in the field describe, cancer by cancer, the progress made and its implications for diagnosis, prognosis and treatment of cancer. The deep impact on the clinics and the challenge for future translational research become evident.

Cancer Genomics

Author : Robert L. Strausberg
ISBN : 1586032518
Genre : Medical
File Size : 84. 33 MB
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This volume explores the genomics of cancer. Contributions explain how advances in biomedical research in the 1990s launched the genomics era - we are no longer satisfied to study a gene or gene product in isolation, but rather we strive to view each gene within the complex circuitry of a cell. In rapid succession, this mindset has invigorated the analysis of all molecular entities, from the genome, to transcripts (transciptome) and proteins (proteome).

Cancer Genomics

Author : Amal M EL-Naggar
ISBN : 9780128061190
Genre : Medical
File Size : 74. 99 MB
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Soft tissue sarcomas (STSs) are a diverse group of uncommon mesenchymally derived malignant tumors and commonly present as an asymptomatic mass almost anywhere in the body. The most important steps in the diagnosis and therefore subsequent management of STSs include adequate tumor biopsies for proper histologic evaluation, including immunohistochemical studies, and detection of disease extension, and radiological imaging. Although STSs are relatively uncommon, they are typically high grade and, if diagnosed at an advanced stage, survival rates for such patients are poor. Although important insights into STS pathogenesis and new molecular diagnostic tools have emerged, prognosis for sarcoma patients with metastatic disease has failed to improve. Identifying those factors that contribute to STS metastasis that could be targeted therapeutically would have a tremendous impact on survival in these diseases. Here we summarize characteristics of some of the more common STS subtypes, as well as known molecular alterations and their roles in sarcomatogenesis.

Cancer Genomics

Author : Angela Greco
ISBN : 9780128061138
Genre : Medical
File Size : 88. 69 MB
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Thyroid cancer represents the most common endocrine malignancy and its incidence is increasing. The majority of thyroid tumours (90–95%) originate from the follicular epithelial cells; it includes several histotypes and related variants characterized by different biological and clinical behavior, such as differentiated papillary and follicular carcinoma (PTC and FTC), and poorly differentiated and anaplastic carcinoma (PDTC and ATC). Medullary thyroid carcinoma (MTC) represents a small fraction of thyroid tumors and originates from the parafollicular C cells. PTCs feature a frequent deregulation of the MAPK pathway, as RET/PTC, TRK, RAS or BRAF oncogenes have been found in about 70% of cases. FTCs are associated with RAS mutations and PAX8/PPARγ oncogenic chromosome rearrangements. PDTCs and ATCs display some alterations occurring in differentiated tumors, as well as other alterations specific of late tumor stages. MTC carry RET or RAS mutations. Here we summarize the molecular alterations detected in each thyroid tumor type, their role in the process of thyroid carcinogenesis, as well as how high-throughput gene expression analyses have contributed to the study of this malignancy.

Illuminating Colorectal Cancer Genomics By Next Generation Sequencing

Author : Khalid El Bairi
ISBN : 3030538206
Genre :
File Size : 41. 76 MB
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This book reviews the potential of next-generation sequencing (NGS) in research on and management of colorectal cancer (CRC), a leading cause of death worldwide and one of the most biologically and clinically heterogeneous cancers. It critically discusses findings from recent large-scale studies, clinical trials and meta-analyses and offers an introduction to the management of CRC in the era of precision medicine. In CRC, dozens of driver and passenger mutations are associated with the malignant transformation of epithelial cells. Consequently, the book discusses recent advances in our understanding of the genetics of CRC as a biomarker, the advent of NGS technologies in modern genomics, and the impact of NGS technology on the management of CRC. Furthermore, it highlights the potential of NGS in the context of liquid biopsy and single-cell sequencing in CRC, as well as its role in shedding light on the link between gut microbiota, immune-checkpoint blockade and CRC. The book concludes with a chapter on the limitations and cost-effectiveness of NGS in CRC. Given its scope, the book will appeal to all those interested in learning about the potential of NGS in advancing CRC research and patient care.

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