Abstract:
:Cancers have a clonal origin, yet their chromosomes and genes are non-clonal or heterogeneous due to an inherent genomic instability. However, the cause of this genomic instability is still debated. One theory postulates that mutations in genes that are involved in DNA repair and in chromosome segregation are the primary causes of this instability. But there are neither consistent correlations nor is there functional proof for the mutation theory. Here we propose aneuploidy, an abnormal number of chromosomes, as the primary cause of the genomic instability of neoplastic and preneoplastic cells. Aneuploidy destabilizes the karyotype and thus the species, independent of mutation, because it corrupts highly conserved teams of proteins that segregate, synthesize and repair chromosomes. Likewise it destabilizes genes. The theory explains 12 of 12 specific features of genomic instability: (1) Mutagenic and non-mutagenic carcinogens induce genomic instability via aneuploidy. (2) Aneuploidy coincides and segregates with preneoplastic and neoplastic genomic instability. (3) Phenotypes of genomically unstable cells change and even revert at high rates, compared to those of diploid cells, via aneuploidy-catalyzed chromosome rearrangements. (4) Idiosyncratic features of cancers, like immortality and drug-resistance, derive from subspecies within the 'polyphyletic' diversity of individual cancers. (5) Instability is proportional to the degree of aneuploidy. (6) Multilateral chromosomal and genetic instabilities typically coincide, because aneuploidy corrupts multiple targets simultaneously. (7) Gene mutation is common, but neither consistent nor clonal in cancer cells as predicted by the aneuploidy theory. (8) Cancers fall into a near-diploid (2 N) class of low instability, a near 1.5 N class of high instability, or a near 3 N class of very high instability, because aneuploid fitness is maximized either by minimally unstable karyotypes or by maximally unstable, but adaptable karyotypes. (9) Dominant phenotypes, because of aneuploid genotypes. (10) Uncertain developmental phenotypes of Down and other aneuploidy syndromes, because supply-sensitive, diploid programs are destabilized by products from aneuploid genes supplied at abnormal concentrations; the maternal age-bias for Down's would reflect age-dependent defects of the spindle apparatus of oocytes. (11) Non-selective phenotypes, e.g., metastasis, because of linkage with selective phenotypes on the same chromosomes. (12) The target, induction of genomic instability, is several 1000-fold bigger than gene mutation, because it is entire chromosomes. The mutation theory explains only a few of these features. We conclude that the transition of stable diploid to unstable aneuploid cell species is the primary cause of preneoplastic and neoplastic genomic instability and of cancer, and that mutations are secondary.
journal_name
IUBMB Lifejournal_title
IUBMB lifeauthors
Duesberg P,Fabarius A,Hehlmann Rdoi
10.1080/15216540410001667902keywords:
subject
Has Abstractpub_date
2004-02-01 00:00:00pages
65-81issue
2eissn
1521-6543issn
1521-6551journal_volume
56pub_type
杂志文章,评审相关文献
IUBMB LIFE文献大全abstract::Hepatitis C virus (HCV) is an enveloped positive-strand RNA virus of the Flaviviridae family. It has a genome of about 9,600 nucleotides encoding a large polyprotein (about 3,000 amino acids) that is processed by cellular and viral proteases into at least 10 structural and nonstructural viral proteins. A novel HCV pro...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1002/iub.201
更新日期:2009-07-01 00:00:00
abstract::Copper has a wide and important role in biological systems, determining conformation and activity of many metalloproteins and enzymes, such as cytochrome oxidase and superoxide dismutase . Furthermore, due to its possible reactivity with nonspecific proteins and toxic effects, elaborate systems of absorption, concentr...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1002/iub.1590
更新日期:2017-04-01 00:00:00
abstract::Small extracellular vesicle (sEV) has precise impacts on tumor microenvironment and play vital functions in intercellular interaction. However, the functional role of sEV miRNA on laryngeal squamous cell carcinoma (LSCC) is largely unresolved. Here, the expression of miR-1246 in LSCC tissues and plasma sEV was examine...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.2274
更新日期:2020-07-01 00:00:00
abstract::Silymarin, which is derived from the seeds of Silybum marianum, has been widely used to prevent and treat liver diseases. In our previous study, we reported that at concentrations above the minimal inhibitory concentration (MIC), silymarin exhibited antifungal activity against Candida albicans by targeting its plasma ...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.1716
更新日期:2018-03-01 00:00:00
abstract::We previously found a novel glycosylphosphatidylinositol (GPI)-anchored glycoprotein designated GPI-80 that modulates complement receptor 3 integrin-dependent adhesion and in vitro transendothelial migration of neutrophils. In this study, we show that antibody-mediated cross-linking of GPI-80 led to rapid tyrosine pho...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1080/713803588
更新日期:2000-01-01 00:00:00
abstract::Altered activity of the proteolytic machine-the 26S proteasome is observed in many disease conditions. Hence, either inhibition or activation of the 26S proteasome is thought to be a novel therapy for treatment of certain diseases such as cancer and neurodegenerative disorders. In this study, we tested the potential o...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.1735
更新日期:2018-05-01 00:00:00
abstract::Treatment of microsomes (preferably enriched with endoplasmic reticulum) isolated from bovine pulmonary artery smooth muscle tissue with the O2*- -generating system (hypoxanthine (HPX) plus xanthine oxidase (XO)), markedly stimulated matrix metalloproteinase-2 (MMP-2) activity and also enhanced Ca2+ ATPase activity an...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1080/1521654041000171335
更新日期:2004-05-01 00:00:00
abstract::In many organisms the processes of DNA replication and recombination are closely linked. For instance, in bacterial and eukaryotic systems, replication forks can become stalled or damaged, in many cases leading to the formation of double stranded breaks. Replication restart is an essential mechanism in which the recom...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1080/15216540310001612237
更新日期:2003-08-01 00:00:00
abstract::Small noncoding RNAs are key controllers of cellular function, and their deregulation can lead to cancer development and metastatic evolution. This review summarizes the most important examples of small RNAs involved in human cancer and discusses their clinical use as biomarkers and drug targets for diagnosis, prognos...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.399
更新日期:2010-12-01 00:00:00
abstract::The complex life cycle of intracellular parasitic protozoans entails multiple rounds of DNA replication and mitosis followed by cytokinesis to release daughter parasites. To gain insights into mitotic events it is imperative to identify the biomarkers that constitute the chromosome segregation machinery in the parasit...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1002/iub.1878
更新日期:2018-08-01 00:00:00
abstract::Calcium-sensing receptor (CaSR) contributes to maintain homeostatic levels of extracellular calcium. In addition, CaSR controls other cellular activities such as proliferation and migration, particularly in cells not related to extracellular calcium homeostasis, potentially by cross-talking with parallel signaling pat...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.1232
更新日期:2013-12-01 00:00:00
abstract::Transfer RNAs require essential maturation steps to become functional. Among them, RNase P removes 5' leader sequences of pre-tRNAs. Although RNase P was long thought to occur universally as ribonucleoproteins, different types of protein-only RNase P enzymes were discovered in both eukaryotes and prokaryotes. Interest...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1002/iub.2062
更新日期:2019-08-01 00:00:00
abstract::Sirolimus(SRL, Rapamune(â), rapamycin) is a highly specific inhibitor of mammalian target of rapamycin (mTOR). Sirolimus exerts its biological activity by inhibiting the serine-threonine kinase mammalian target of rapamycin (mTOR), which regulates important cellular processes such as control of cell cycle, cell size, ...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1080/15216540701646484
更新日期:2007-11-01 00:00:00
abstract::Heart disease is the most common cause of morbidity and mortality in Western society and the incidence is projected to increase significantly over the next few decades as our population ages. Heart failure occurs when the heart is unable to pump blood at a rate to commensurate with tissue metabolic requirements and re...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1080/15216540214312
更新日期:2002-08-01 00:00:00
abstract::Bovine Spongiform Encephalopathy (BSE) is typical of the dementias that affect both animals and man; Scrapie in sheep, Creutzfeldt-Jakob disease in man. Global efforts have been made to determine the nature of the active agents in these diseases. At present the 'protein only hypothesis' of Prusiner holds. It was a sur...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1080/15216540500097152
更新日期:2005-04-01 00:00:00
abstract::Deletion of tumor suppressor gene, lethal(2)giant larvae [l(2)gl], leads to brain tumor in Drosophila melanogaster at larval stage of development and severe brain dysplasia in mice. We have studied the effect of two potential antitumor drugs artemisinin and curcumin in the perspective of inhibiting l(2)gl brain tumor....
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.1284
更新日期:2014-07-01 00:00:00
abstract::Cancer related inflammation (CRI) is now recognized as the seventh hallmark in the pathogenesis of many types of malignancies. Paeonol, a natural phenolic component isolated from the root bark of Paeonia moutan, has significant anti-inflammatory activity. Recently, accumulating body of research has revealed potent ant...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.1435
更新日期:2015-10-01 00:00:00
abstract::We investigated the rosiglitazone (RSG) effect on adriamycin (ADM)-induced cardio toxicity in experimental animals. Forty adult Wistar male rats were separated into four groups as follows: normal control; RSG (10 mg/kg)-treated; ADM (10 mg/kg)-administered; and ADM (10 mg/kg) + RSG (10 mg/kg)-treated. Serum lipid leve...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.2190
更新日期:2020-04-01 00:00:00
abstract::Combining two analytical techniques, HPLC and liquid secondary ion mass spectrometry, the orientation of liposomal membrane-bound melittin was analyzed through its trypsin-digested products. We found that trypsin can access all proteolytic sites of the membrane-bound melittin when the liposomes have no transmembrane p...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1080/152165400300001543
更新日期:2000-09-01 00:00:00
abstract::The aggressive biological behavior of invasive and metastatic cancer is considered to be the most insidious and life-threatening aspect for breast cancer patients. It is mostly the result of changes in many molecular characteristics of tumor cells, including alterations in gene expression and the balance of proteolyti...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1080/15216540701395074
更新日期:2007-06-01 00:00:00
abstract::In protein and RNA macromolecules, only a limited number of different side-chain chemical groups are available to function as catalysts. The myriad of enzyme-catalyzed reactions results from the ability of most of these groups to function either as nucleophilic, electrophilic, or general acid-base catalysts, and the k...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1080/15216540211468
更新日期:2002-02-01 00:00:00
abstract::Upregulation of haptoglobin (Hp) expression in the rat during the acute phase (AP) response is the result of synergistic effects of IL-6-, IL-1beta-, and corticosterone-activated signaling pathways. IL-6 signaling terminates in cis-trans interactions of the Hp gene hormone-responsive element (HRE) with transcription f...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.313
更新日期:2010-03-01 00:00:00
abstract::How should a protein be designed to serve in processes as diverse as chromosome condensation, sister chromatid cohesion, DNA recombination, gene dosage regulation, and perhaps even gene silencing or transcriptional regulation--which occur in both mitosis and meiosis? Such a protein or protein complex needs to bear DNA...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1080/15216540310001639661
更新日期:2003-12-01 00:00:00
abstract::Various strategies have been applied to replace the loss of cardiomyocytes in order to restore reduced cardiac function and prevent the progression of heart disease. Intensive research efforts in the field of cellular reprogramming and cell transplantation may eventually lead to efficient in vivo applications for the ...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1002/iub.2150
更新日期:2020-01-01 00:00:00
abstract::Cell-surface-bound extracellular DNA (csbDNA) is present on the outer membrane of blood cells, including both red blood cells and leukocytes. Although less well characterized than cell-free DNA (cfDNA) in plasma and serum, leukocyte and red blood cell csbDNA form a considerable fraction of the blood extracellular nucl...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1002/iub.2070
更新日期:2019-09-01 00:00:00
abstract::In tsRSV-infected NRK (tsNRK) cells, pp60(v-src) reactivation by temperature-shift from a nonpermissive temperature, 39 C, to a permissive one, 32 degrees C, induced the production of inositol phosphates (IPt) and phosphatidylethanol (PEt). This was accompanied by an increase in membrane-associated protein kinase C (P...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1080/713803467
更新日期:1999-07-01 00:00:00
abstract::In this article, the experiments used to construct the ambient pH-signaling network involved in the secretion of enzymes by filamentous fungi have been reviewed, focusing on the phosphate-repressible phosphatases in Aspergillus nidulans. Classic and molecular genetics have been used to demonstrate that proteolysis of ...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.1217
更新日期:2013-11-01 00:00:00
abstract::During the hand plate development, the processes of cell differentiation and control of cell death are relevant to ensure a correct shape of the limb. The progenitor cell pool that later will differentiate into cartilage to form the digits arises from undifferentiated mesenchymal cells beneath the apical ectodermal ri...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1002/iub.563
更新日期:2011-10-01 00:00:00
abstract::Recent successes in identifying the genes and associated proteins underlying several familial neurodegenerative conditions have not always resulted in accounts as to why the associated patterns of neuronal damage are so specific and limited. Here, with reference to Huntington's disease, we present a general scheme to ...
journal_title:IUBMB life
pub_type: 杂志文章,评审
doi:10.1080/1521654031000153012
更新日期:2003-06-01 00:00:00
abstract::Myocardial ischemia/reperfusion (I/R) injury greatly contributes to myocardial tissue damage in patients with coronary disease, which eventually leads to heart failure. Long noncoding RNAs (lncRNAs) have an emerging role in the process of myocardial I/R injury. Our previous work revealed the protective role of miR-374...
journal_title:IUBMB life
pub_type: 杂志文章
doi:10.1002/iub.2428
更新日期:2020-12-09 00:00:00