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High Throughput Analysis Of The Human Mitochondrial Genome Reveals Its Dynamics Function And Signals Of Selection In Cancer
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Book Synopsis High-throughput Analysis of the Human Mitochondrial Genome Reveals Its Dynamics, Function, and Signals of Selection in Cancer by : Sneha Grandhi
Download or read book High-throughput Analysis of the Human Mitochondrial Genome Reveals Its Dynamics, Function, and Signals of Selection in Cancer written by Sneha Grandhi and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Known as the energy powerhouses of the cell, mitochondria carry their own genomes, and encode for key cellular respiration proteins. Carrying multiple copies per cell, a given mitochondrial DNA (mtDNA) variant can be present at varying proportions, termed heteroplasmy. MtDNA is acquired exclusively through maternal inheritance and becomes stochastically replicated and segregated into dividing mitochondria over an organism's lifespan. An individual's constellation of mtDNA variants and their respective heteroplasmy levels can therefore change in response to selective pressures in somatic cells and/or selection that takes place during germline transmission. MtDNA aberrations are associated with many disorders, including cancer. Although mitochondrial genomes accumulate elevated mutation rates in cancer cells, the origin and functional impact of these mutations remain controversial. Here, we queried whole-genome sequencing data from 1,916 patients across 24 cancer types to characterize patterns of mtDNA mutations and elucidate the selective constraints driving their fate. We also tracked changes in per-cell abundances of mtDNA mutations from normal to tumor cells in the same patient. Tumor mitochondrial genomes show distinct mutational patterns and are disproportionately enriched for protein-altering changes. Moreover, protein-altering mtDNA variants that are initially present at low frequencies in normal cells preferentially expand in the altered tumor environment, suggesting selective advantage. Renal chromophobe and thyroid cancers show strong signals of positive selection with higher proportions and per-cell abundances of truncating mtDNA variants. Dramatic tumor- and tissue-specific variations in selective pressures suggest that cancer cells with advantageous levels of damaged mitochondrial genomes will selectively proliferate to facilitate the tumorigenic process.We also cataloged mitochondrial sequence variants and gene expression across 927 cancer cell lines from the Cancer Cell Line Encyclopedia (CCLE). We used this data to create a novel computational method called DoReMi (Donor, Recipient Mitochondrial DNA matching). DoReMi scores candidate mtDNA donor and recipient cell lines for cybridization experiments, which help identify the role of mtDNA variants in-vitro under a controlled nuclear genetic background. This tool allows researchers to design optimized cybrid experiments for querying the role of mutations in their mitochondrial-encoded gene of interest. Researchers may also apply DoReMi to study their own cell lines of interest.
Book Synopsis Investigation of human mitochondrial DNA abnormality in colon cancer by : Mansoureh Akouchekian
Download or read book Investigation of human mitochondrial DNA abnormality in colon cancer written by Mansoureh Akouchekian and published by Cuvillier Verlag. This book was released on 2008-10-07 with total page 92 pages. Available in PDF, EPUB and Kindle. Book excerpt: The appearance of mtDNA abnormalities including deletions, duplications, insertions or combinations of them in colorectal cancer (CRC) patients was investigated in this work. Our result showed that 11 of 90 CRC patients had a 8.7 kb mtDNA deletion (12.2%) while this deletion was not found in 33 healthy controls. (P=0.035) We conclude that the 8.7 kb deletion can be a secondary effect of the cancer process, which is not inherited. This is the first report on large scale deletions in CRC. We also analyzed the correlation between cancers and mitochondrial haplogroups. The relationship between CRC and each of 9 major mitochondrial haplogroups were examined in Iranian CRC patients. This is the first study to trace mtDNA HVSI variants in CRC patients of the Persian population. Our data showed that patients with CRC have a significantly (P=0.001) higher frequency of haplogroup K (9.5%) when compared with controls (0%). The mitochondrial polymorphisms in haplogroup K might play a causative role in predisposing to CRC. Variations in the D-loop region were found in both CRC patients and healthy people but the frequency of SNPs in CRC patients was higher than in control samples. We found 13 new polymorphisms that had not been recorded in the mitochondrial database. We also detected one T→C transition at np16519 in 28 out of 40 patients (70%). In a recent study researchers reported that the T16519C variation worsen the outcome of pancreatic cancer patients, possibly because it is involved in altering cellular metabolism. Because we found this mutation frequently in our healthy controls (43%) and could not find any differentiation among our patients with respect to the alleles at this mutation, we conclude that the functional significance of this mutation needs further investigation. We also analyzed somatic mutations in mitochondrial genes encoding subunits of the respiratory complex I. Seven somatic mutations in the MT-ND1 gene were found. Six of these mutations were synonymous mutations. The T4216C mutation that was detected in 26% of the CRC tested samples resulted in the substitution of tyrosine with the amino acid histidine at amino acid position 304. The T4216C mutation was recently reported in LHON patients (Povalko et al., 2005). The patients in our study who carried the T4216C mutation had no known vision problems. It is difficult to speculate about the role of this mutation in CRC. LHON mutations were shown to affect complex I in mitochondria and other investigators found other mutations in different parts of this gene. To show pathogenicity of this mutation or find its role in cancer, more investigations particularly in mtDNA of LHON patients are needed. Because cancer is a multifactorial disease and a causative mutation which leads to blindness and cancer has not been reported, we conclude that this mutation may be a secondary effect or rare polymorphism.
Book Synopsis DNA Helicases and DNA Motor Proteins by : Maria Spies
Download or read book DNA Helicases and DNA Motor Proteins written by Maria Spies and published by Springer Science & Business Media. This book was released on 2012-11-19 with total page 308 pages. Available in PDF, EPUB and Kindle. Book excerpt: In recent years, a number of groundbreaking structural and mechanistic studies deepened our understanding of helicase mechanisms and established new approaches for their analyses. Many fundamental mechanistic questions ranging from the mechanism of force generation, mechanochemical coupling to distinct mechanisms by which the same enzyme translocates on DNA removing obstacles, unwinds DNA and/or remodels nucleoprotein complexes, however, remain to be answered. It is even less understood how the helicase motors are incorporated into a wide range of genome maintenance and repair machines. The field has reached a stage when the studies of molecular mechanisms and basic biology of helicases can and shall be integrated with the studies of development, cancer and longevity. The objective of this book is to provide the first systematic overview of structure, function and regulation of DNA helicases and related molecular motors. By integrating the knowledge obtained through the diverse technical approaches ranging from single-molecule biophysics to cellular and molecular biological studies the editors aim to provide a unified view on how helicases function in the cell, are regulated in response to different cellular stresses and are integrated into large macromolecular assemblies to form a complex and adaptive living system.
Download or read book Mitochondrial Gene Expression written by and published by . This book was released on 2021 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Signal Transduction in Cancer by : David A. Frank
Download or read book Signal Transduction in Cancer written by David A. Frank and published by Springer Science & Business Media. This book was released on 2002-12-31 with total page 358 pages. Available in PDF, EPUB and Kindle. Book excerpt: One of the most exciting areas of cancer research now is the development of agents which can target signal transduction pathways that are activated inappropriately in malignant cells. The understanding of the molecular abnormalities which distinguish malignant cells from their normal counterparts has grown tremendously. This volume summarizes the current research on the role that signal transduction pathways play in the pathogenesis of cancer and how this knowledge may be used to develop the next generation of more effective and less toxic anticancer agents. Series Editor comments: "The biologic behavior of both normal and cancer cells is determined by critical signal transduction pathways. This text provides a comprehensive review of the field. Leading investigators discuss key molecules that may prove to be important diagnostic and/or therapeutic targets."
Download or read book Molecular Biology of the Cell written by and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Telomeres and Telomerase in Cancer by : Keiko Hiyama
Download or read book Telomeres and Telomerase in Cancer written by Keiko Hiyama and published by Springer Science & Business Media. This book was released on 2009-03-18 with total page 375 pages. Available in PDF, EPUB and Kindle. Book excerpt: Telomerase, an enzyme that maintains telomeres and endows eukaryotic cells with immortality, was first discovered in tetrahymena in 1985. In 1990s, it was proven that this enzyme also plays a key role in the infinite proliferation of human cancer cells. Now telomere and telomerase are widely accepted as important factors involved in cancer biology, and as promising diagnostic tools and therapeutic targets. Recently, role of telomerase in “cancer stem cells” has become another attractive story. Until now, there are several good books on telomere and telomerase focusing on biology in ciliates, yeasts, and mouse or basic sciences in human, providing basic scientists or students with updated knowledge.
Book Synopsis Evolution of Translational Omics by : Institute of Medicine
Download or read book Evolution of Translational Omics written by Institute of Medicine and published by National Academies Press. This book was released on 2012-09-13 with total page 354 pages. Available in PDF, EPUB and Kindle. Book excerpt: Technologies collectively called omics enable simultaneous measurement of an enormous number of biomolecules; for example, genomics investigates thousands of DNA sequences, and proteomics examines large numbers of proteins. Scientists are using these technologies to develop innovative tests to detect disease and to predict a patient's likelihood of responding to specific drugs. Following a recent case involving premature use of omics-based tests in cancer clinical trials at Duke University, the NCI requested that the IOM establish a committee to recommend ways to strengthen omics-based test development and evaluation. This report identifies best practices to enhance development, evaluation, and translation of omics-based tests while simultaneously reinforcing steps to ensure that these tests are appropriately assessed for scientific validity before they are used to guide patient treatment in clinical trials.
Book Synopsis Cancer Cell Lines Part 1 by : John Masters
Download or read book Cancer Cell Lines Part 1 written by John Masters and published by Springer Science & Business Media. This book was released on 2006-04-11 with total page 295 pages. Available in PDF, EPUB and Kindle. Book excerpt: Continuous cell lines derived from human cancers are the most widely used resource in laboratory-based cancer research. The first 3 volumes of this series on Human Cell Culture are devoted to these cancer cell lines. The chapters in these first 3 volumes have a common aim. Their purpose is to address 3 questions of fundamental importance to the relevance of human cancer cell lines as model systems of each type of cancer: 1. Do the cell lines available accurately represent the clinical presentation? 2. Do the cell lines accurately represent the histopathology of the original tumors? 3. Do the cell lines accurately represent the molecular genetics of this type of cancer? The cancer cell lines available are derived, in most cases, from the more aggressive and advanced cancers. There are few cell lines derived from low grade organ-confined cancers. This gap can be filled with conditionally immortalized human cancer cell lines. We do not know why the success rate for establishing cell lines is so low for some types of cancer and so high for others. The histopathology of the tumor of origin and the extent to which the derived cell line retains the differentiated features of that tumor are critical. The concept that a single cell line derived from a tumor at a particular site is representative of tumors at that site is naïve and misleading.
Book Synopsis Techniques to Investigate Mitochondrial Function in Neurons by : Stefan Strack
Download or read book Techniques to Investigate Mitochondrial Function in Neurons written by Stefan Strack and published by Humana. This book was released on 2017-03-18 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume describes a broad spectrum of experimental approaches for investigating structure, function, and transport of neuronal mitochondria in health and disease. Most of these approaches were only recently developed and range from electron tomography-based 3D reconstruction of mitochondrial cristae to patch clamp recording from mitochondria in intact neurons. The chapters in this book cover topics such as mitochondrial proteomics, fluorescence lifetime imaging, respirometry and mitophagy, as well as optical approaches based on the use of genetically engineered fluorescent sensors for monitoring synaptic ATP and axonal ROS generation, mitochondrial Ca2+ cycling and pH changes, and mitochondrial dynamics and axonal trafficking in live neurons. Each chapter also discusses difficulties, tips, tricks, and precautions to take. Neuromethods series style chapters include the kind of detail and key advice from the specialists needed to get successful results in your laboratory. Cutting-edge and comprehensive, Techniques to Investigate Mitochondrial Function in Neurons is a valuable and useful resource for a broad range of investigators interested in the function of neuronal mitochondria in health and disease states.
Book Synopsis Mammography and Beyond by : National Research Council
Download or read book Mammography and Beyond written by National Research Council and published by National Academies Press. This book was released on 2001-07-23 with total page 311 pages. Available in PDF, EPUB and Kindle. Book excerpt: Each year more than 180,000 new cases of breast cancer are diagnosed in women in the U.S. If cancer is detected when small and local, treatment options are less dangerous, intrusive, and costly-and more likely to lead to a cure. Yet those simple facts belie the complexity of developing and disseminating acceptable techniques for breast cancer diagnosis. Even the most exciting new technologies remain clouded with uncertainty. Mammography and Beyond provides a comprehensive and up-to-date perspective on the state of breast cancer screening and diagnosis and recommends steps for developing the most reliable breast cancer detection methods possible. This book reviews the dramatic expansion of breast cancer awareness and screening, examining the capabilities and limitations of current and emerging technologies for breast cancer detection and their effectiveness at actually reducing deaths. The committee discusses issues including national policy toward breast cancer detection, roles of public and private agencies, problems in determining the success of a technique, availability of detection methods to specific populations of women, women's experience during the detection process, cost-benefit analyses, and more. Examining current practices and specifying research and other needs, Mammography and Beyond will be an indispensable resource to policy makers, public health officials, medical practitioners, researchers, women's health advocates, and concerned women and their families.
Book Synopsis Mitochondrial DNA and Diseases by : Hongzhi Sun
Download or read book Mitochondrial DNA and Diseases written by Hongzhi Sun and published by Springer. This book was released on 2017-11-25 with total page 233 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book describes molecular principles and mechanisms by which mitochondrial DNA (mtDNA) can drive the occurrence of diseases and the latest understanding of mtDNA biology. The book explores roles of mtDNA mutation and genetic changes in cancer, with a special focus on lung cancer, and the significance of approach, application, and bioethics of mtDNA sequencing. Authors made a great effort to overview roles of mtDNA signaling pathways, base excision repair, methylation, USP30-mediated regulation, mitochondrial ribosome, autophagy pathways, or ROS-dependent signaling in the pathogenesis, diagnosis, prevention and treatment of diseases. It also demonstrates the importance of basic mitochondrial genetics and the relationship between mutations and disease phenotypes and ageing. This book covers not only the basic information of mtDNA, the relationship of mtDNA and disease, but also mtDNA in stem cell and mitochondria and metabolism etc. The book is written for biological and clinical students and researchers in the field of mtDNA–associated diseases.
Book Synopsis Clinical Mitochondrial Medicine by : Patrick F. Chinnery
Download or read book Clinical Mitochondrial Medicine written by Patrick F. Chinnery and published by Cambridge University Press. This book was released on 2018-05-17 with total page 229 pages. Available in PDF, EPUB and Kindle. Book excerpt: This interactive clinical textbook takes a system- and case-based approach in understanding mitochondrial disorders in clinical practice.
Book Synopsis Protein Tyrosine Phosphatases in Cancer by : Benjamin G. Neel
Download or read book Protein Tyrosine Phosphatases in Cancer written by Benjamin G. Neel and published by Springer. This book was released on 2016-08-05 with total page 362 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book aims to bridge the gap in understanding how protein-tyrosine phosphatases (PTPs), which carry out the reverse reaction of tyrosine phosphorylation, feature in cancer cell biology. The expertly authored chapters will first review the general features of the PTP superfamily, including their overall structure and enzymological properties; use selected examples of individual PTP superfamily members, to illustrate emerging data on the role of PTPs in cancer; and will review the current status of PTP-based drug development efforts. Protein Tyrosine Phosphatases in Cancer,from renowned researchers Benjamin Neel and Nicholas Tonks, is invaluable reading for researchers in oncology, stem cell signaling,and biochemistry.
Book Synopsis Mitochondrial DNA by : Herve Seligmann
Download or read book Mitochondrial DNA written by Herve Seligmann and published by BoD – Books on Demand. This book was released on 2018-10-31 with total page 226 pages. Available in PDF, EPUB and Kindle. Book excerpt: The very short genomes of mitochondria summarize the complexity of molecular biology and its interactions with cellular and whole organism biology. Studies of mitogenomes contribute to the understanding of molecular biology and evolution, and to health management. Despite or even due to their small sizes, mitogenomes continue to surprise us. Studies of mitogenomes reveal the details of molecular organization and its evolution under constraints for miniaturization.
Book Synopsis Cancer Evolution by : Charles Swanton
Download or read book Cancer Evolution written by Charles Swanton and published by Perspectives Cshl. This book was released on 2017 with total page 350 pages. Available in PDF, EPUB and Kindle. Book excerpt: Tumor progression is driven by mutations that confer growth advantages to different subpopulations of cancer cells. As a tumor grows, these subpopulations expand, accumulate new mutations, and are subjected to selective pressures from the environment, including anticancer interventions. This process, termed clonal evolution, can lead to the emergence of therapy-resistant tumors and poses a major challenge for cancer eradication efforts. Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine examines cancer progression as an evolutionary process and explores how this way of looking at cancer may lead to more effective strategies for managing and treating it. The contributors review efforts to characterize the subclonal architecture and dynamics of tumors, understand the roles of chromosomal instability, driver mutations, and mutation order, and determine how cancer cells respond to selective pressures imposed by anticancer agents, immune cells, and other components of the tumor microenvironment. They compare cancer evolution to organismal evolution and describe how ecological theories and mathematical models are being used to understand the complex dynamics between a tumor and its microenvironment during cancer progression. The authors also discuss improved methods to monitor tumor evolution (e.g., liquid biopsies) and the development of more effective strategies for managing and treating cancers (e.g., immunotherapies). This volume will therefore serve as a vital reference for all cancer biologists as well as anyone seeking to improve clinical outcomes for patients with cancer.
Book Synopsis Tumor Suppressor Genes in Human Cancer by : David E. Fisher
Download or read book Tumor Suppressor Genes in Human Cancer written by David E. Fisher and published by Springer Science & Business Media. This book was released on 2000-10-26 with total page 441 pages. Available in PDF, EPUB and Kindle. Book excerpt: David Fisher, MD, PhD, and an authoritative panel of academic, cutting-edge researchers review and summarize the current state of the field. Describing the broad roles of tumor suppressors from a perspective based in molecular biology and genetics, the authors detail the major suppressors and the pathways they regulate, including cell cycle progression, stress responses, apoptosis, and responses to DNA damage. Leading-edge and forward-looking, Tumor Suppressor Genes in Human Cancer illuminates what is currently known of tumor suppressor genes and their regulation, work that is already beginning to revolutionize cancer target elucidation, drug discovery, and treatment design.
