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Genomic Instability

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An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.

Also Known As:

Genome Instability; Genome Stability; Genomic Stability; Genome Instabilities; Genome Stabilities; Genomic Instabilities; Genomic Stabilities; Instabilities, Genome; Instabilities, Genomic; Instability, Genome; Instability, Genomic; Stabilities, Genome; Stabilities, Genomic; Stability, Genome; Stability, Genomic

Networked: 4551 relevant articles (30 outcomes, 274 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Neoplasms (Cancer)
2.	Carcinoma (Carcinomatosis)
3.	Microsatellite Instability
4.	Lung Neoplasms (Lung Cancer)
5.	Premature Aging

Experts

1.	Fenech, Michael: 26 articles (10/2015 - 07/2002)
2.	Aguilera, Andrés: 23 articles (11/2015 - 08/2003)
3.	Brosh, Robert M: 21 articles (11/2015 - 10/2002)
4.	Bohr, Vilhelm A: 21 articles (11/2014 - 05/2002)
5.	Jackson, Stephen P: 16 articles (01/2016 - 05/2002)
6.	Hickson, Ian D: 16 articles (04/2015 - 11/2002)
7.	Alt, Frederick W: 15 articles (06/2013 - 06/2002)
8.	Zempleni, Janos: 14 articles (06/2014 - 11/2006)
9.	Kovalchuk, Olga: 14 articles (07/2013 - 04/2004)
10.	Thomas, Philip: 13 articles (10/2015 - 01/2004)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Genomic Instability:

1.	DNA (Deoxyribonucleic Acid)IBA 01/01/2015 - "Hence, techniques that aid in the easy identification of such non-B DNA motifs will prove to be very useful in determining factors responsible for genomic instability. " 12/22/2015 - "In this study, we address this paradox by identifying the DNA helicase RECQL5 as a suppressor of genomic instability in MPNs. " 09/20/2015 - "In this study, we found that OGT and OGT mediated H2B S112 GlcNAcylation are involved in DNA damage response for maintaining genomic stability and are required for resistance to many DNA-damaging and replication stress-inducing agents. " 07/01/2015 - "The results of this study indicate that exposing JCV ST-positive cells to DNA-damaging agents causes genomic instability, which contributes to carcinogenesis. " 05/01/2015 - "Recent studies suggested that RECQL is involved in DNA double-strand break repair and it plays an important role in the maintenance of genomic stability. "
2.	Telomerase (Telomerase Reverse Transcriptase)IBA 01/01/2015 - "As G-quadruplex studies have progressed, its significant roles in a variety of biological process have been revealed, including telomerase activity, genome stability, DNA replication, and oncogene expression. " 06/08/2006 - "This study suggests that the type of genomic instability in human cells may depend critically on whether they are telomerase-positive or -negative and that their sensitivities to metals could depend on whether they are clustered or diffuse." 12/01/2015 - "Telomerase reverse transcriptase (TERT), one of the main functional subunits of the telomerase, is an important factor in modulating telomerase activity, telomere length, and genomic stability. " 01/01/2015 - "In addition to demonstrating that dysfunctional telomeres contribute to IR-induced mutation frequencies and genome instability, we reveal non-canonical roles for telomerase, in that telomerase activity was required for IR-induced enrichment of mammary epithelial putative stem/progenitor cell populations, a finding also suggestive of cellular reprograming. " 01/01/2015 - "The representative data show that telomerase reactivation in the backdrop of genomic instability induced by telomere dysfunction can greatly enhance tumorigenesis. "
3.	Proteins (Proteins, Gene)IBA 08/01/2013 - "The functions of most of these proteins are not yet known, but they are generally assumed to play roles in development, genome stability and/or protection against viruses. " 11/01/2012 - "Given the high level of conservation of key proteins like RecA and the conservation of the principles of action of all recombination proteins, the deep knowledge acquired during decades of studies of homologous recombination in bacteria is the foundation of our present understanding of the processes that govern genome stability and evolution in all living organisms. " 04/01/2006 - "Specifically, prior studies suggest that a delicate balance exists in Ku expression, as overexpression of Ku proteins promotes oncogenic phenotypes, including hyperproliferation and resistance to apoptosis; whereas deficient or low expression of Ku leads to genomic instability and tumorigenesis. " 01/01/1999 - "Epidemiological and in vitro-studies have shown that some of the genital HPV types, the high risk-types 16, 18, 31 etc., code for proteins (E6/E7) which strongly influence the cell cycle and genome stability. " 10/01/1998 - "The application of new technologies for identifying interacting proteins has connected the studies on topoisomerases to other areas of human biology including genome stability and aging. "
4.	ChromatinIBA 10/01/2014 - "The test system has been improved in the last years, i.e., it was shown that, apart from MN also other nuclear anomalies can be evaluated in UDC which are found in other types of epithelial cells as well (e.g., in oral and nasal cells) and are indicative for acute toxicity (pyknosis, karyorrhexis, karyolysis, condensed chromatin) and genomic instability (nuclear buds, binucleates). " 10/01/2014 - "The purpose of the present study was to evaluate the genomic instability in BC patients by means of buccal cells micronucleus (MN) cytome assay Methods: The frequencies of nuclear anomalies including MN, binucleates (BN), broken eggs (BE), condensed chromatin (CC), karyorrhexis (KR) and karyolysis (KL) were evaluated in exfoliated buccal mucosa cells of Mexican women with primary BC and healthy women. " 05/15/2010 - "Studies on chromatin modification during oocyte development will have implications for our understanding of the mechanisms controlling nuclear architecture and genomic stability in female germ line." 01/01/2008 - "Recent studies suggest that chromatin modifying factors play a critical role in the maintenance of genomic stability. " 06/01/2007 - "In the yeast Saccharomyces cerevisiae, the highly repetitive structure of this locus makes it a very interesting target for studies about genome stability, chromatin-mediated transcriptional silencing and progression of aging. "
5.	Folic Acid (Vitamin M)FDA LinkGeneric 04/02/2010 - "We investigated the hypotheses that the genomic instability observed under conditions of folate deficiency in other cell types extends to skin, adversely effecting cellular capacity to handle UVR insult and that optimizing folate levels in skin is beneficial in preventing or repairing the pro-carcinogenic effects of UVR exposure. " 11/01/2004 - "Evidence from animal and human studies is presented here in support of folate acting to maintain genomic stability through both these mechanisms." 09/01/2015 - "Folate deficiency can lead to mutations and genome instability, and has been shown to exacerbate the genotoxic potential of environmental toxins. " 03/01/2014 - "The lack of association between inadequate folate intake, folate deficiency and mitochondrial genomic instability was confirmed also considering reference values of folate based on DNA damage prevention. " 03/01/2014 - "Folic acid plays an important role in the maintenance of genomic stability in mammals. "
6.	N-methylsuccinimideIBA 09/04/1997 - "The results of this study suggest that 45% (18 out of 40) showed genomic instability at a minimum of 1 locus; 4 cases each showed MSI at one and 2 loci, 4 cases had MSI at 3 loci, 3 cases showed MSI at 5 loci, while one case each showed MSI at 7, 8 and 15 loci. " 11/14/2013 - "We aimed to carry out an analysis of gland level genomic instability for MSI and promoter methylation. " 01/01/2009 - "Genomic instability (MSI and LOH) in both epithelia and stroma appeared after around 40 years of age and remained relatively constant thereafter at relatively low frequencies (4.8-30.4%). " 07/01/2007 - "The absence of MSI in our cases could be due to the need for a longer period of BE before genomic instability develops, or MSI may only arise in a proportion of patients. " 01/01/2004 - "Our data suggest that CIN and MSI contribute to the genomic instability in GBMs via independent pathways. "
7.	Proliferating Cell Nuclear Antigen (PCNA)IBA 10/23/2014 - "In conclusion, our study suggests that YB-1 functions as a PCNA-interacting factor to exert its regulatory role on the MMR process and involves in the induction of genome instability, which may partially account for the oncogenic potential of YB-1. " 06/01/2012 - "Here, we have used gene-targeted mouse embryonic fibroblasts to perform a comprehensive study of the in vivo roles of PCNA-Ub and of the Y family TLS Pols η, ι, κ, Rev1 and the B family TLS Polζ in TLS and in the suppression of DNA damage signaling and genome instability after exposure to UV light. " 05/01/2011 - "In this study, we demonstrated a novel tumour suppressive function of ING1b in preserving genomic stability upon replication stress through regulating PCNA monoubiquitination. " 03/01/2014 - "Further, it was also shown that Ing1b protected the cells from genomic instability induced cell death by promoting ubiquitination of proliferating cell nuclear antigen (PCNA). " 08/15/2013 - "In this Review, we summarize the evidence that Elg1/ATAD5-RLC acts as a PCNA unloader and discuss the still enigmatic relationship between the function of Elg1/ATAD5-RLC in PCNA unloading and the role of Elg1/ATAD5 in maintaining genomic stability. "
8.	Phosphotransferases (Kinase)IBA 09/01/2015 - "LAMMER kinase contributes to genome stability in Ustilago maydis." 01/01/2015 - "The mitotic checkpoint kinase Mps1 was selected to explore whether enhancement in genomic instability is a viable therapeutic strategy. " 01/01/2015 - "ATM kinase preserves genomic stability by acting as a tumour suppressor. " 10/01/2014 - "Moreover, oxidative stress generates high genome instability in GSH-depleted cells, but does not activate the checkpoint kinase Rad53. " 06/12/2014 - "BRCA2 coordinates the activities of cell-cycle kinases to promote genome stability."
9.	EnzymesIBA 12/01/2015 - "Deregulation of these SUMOylation and deSUMOylation enzymes causes severe defects in cell proliferation and genome stability. " 11/01/2015 - "Type 1A topoisomerases (topos) are ubiquitous enzymes involved in supercoiling regulation and in the maintenance of genome stability. " 11/01/2014 - "This review focuses on the roles that recombination enzymes play in underpinning genome duplication, aiding replication fork movement in the face of the many replisome barriers that challenge genome stability. " 04/22/2014 - "Understanding the regulation of enzymes that regulate H3K56 acetylation is of great interest, because the loss of H3K56 acetylation leads to genomic instability. " 03/01/2013 - "Emerging functions for this unique family of enzymes include roles in genomic stability, angiogenesis, metabolism, and anoikis. "
10.	Free RadicalsIBA 04/01/2004 - "In this paper, we analyzed the genome stability of several plant mutants impaired in the protection against free radicals. " 07/01/2005 - "Irradiation causes a variety of lesions in important biomolecules of the cell through generation of free radicals leading to genomic instability. " 08/22/2001 - "The resulting genomic instability is proposed to be due to free radicals and/or to the unscheduled "switching-on" of signal transduction pathways." 01/15/1998 - "These results may be explained by an altered response to damage induced by free radicals, and suggest that PARP limits genomic instability from such damage." 07/01/2003 - "Our study demonstrates that AME at 5 microg/ml protected HPBLs against radiation-induced DNA damage and genomic instability and its radioprotective activity may be by scavenging of radiation-induced free radicals and increased oxidant status."

Therapies and Procedures

1.	Drug Therapy (Chemotherapy) 10/09/2013 - "Analyzing the underlying mechanism and pathways involved in preventing the cells from secreting bystander signals will provide new insights that can be applied to inhibit these mechanisms in other cell types, thereby preventing and controlling the bystander response and genomic instability and increasing the therapeutic gain in chemotherapy. " 10/02/2009 - "We demonstrate that radiation and chemotherapy bystander responses induce early genomic instability coupled with defects in mitochondrial function. " 10/02/2009 - "Radiation and chemotherapy bystander effects induce early genomic instability events: telomere shortening and bridge formation coupled with mitochondrial dysfunction." 10/22/2007 - "In these tumours with an altered control of genomic stability, accumulation of chemotherapy-induced genetic alterations may contribute to cell death and account for complete response. " 06/01/2007 - "Consequently, p53 mutations increase cell proliferation and survival, and in some settings promote genomic instability and resistance to certain chemotherapies. "
2.	Radiotherapy 06/06/2005 - "Thus, in this study, genomic instability was not associated with radiotherapy in those who had received such treatment, nor was it found to be a transgenerational radiation effect." 01/10/2013 - "This work may assign a new deleterious role to breast CSCs in aggressive recurrence after radiotherapy, as the transmitted genomic instability potentially leads tumour cells to acquire more aggressive characteristics." 02/10/2011 - "Yet, serum from Hiroshima survivors, Chernobyl liquidators and radiotherapy patients can induce a clastogenic effect on naive cells, showing indirect induction of genomic instability that persists years after exposure. " 08/01/2010 - "Talks covered genomic instability (its importance for radiation-induced carcinogenesis and potential for exploitation in the development of novel chemoradiotherapy combinations) and the prospects of exploiting knowledge of the genome to understand how individual genetic variation can impact on a patient's likelihood of developing toxicity following radiotherapy. " 05/01/2001 - "The potential contribution of induced genomic instability to tumour and normal tissue response, and second tumours, after radiotherapy, is explored. "
3.	Vegetarian Diet (Vegetarianism) 10/01/2015 - "These data suggest that the vegetarian diet might be beneficial in lowering genomic instability in healthy individuals. " 02/01/2004 - "Does a vegetarian diet influence genomic stability?"
4.	Lasers (Laser) 10/01/2012 - "To analyze the roles of exposures during gestation and conception on genomic stability in the offspring, stability was assessed via the Comet assay and highly sensitive, semiautomated confocal laser scans of γH2AX foci in cord, maternal, and paternal blood as well as spermatozoa from 39 families in Crete, Greece, and the United Kingdom. " 01/01/1994 - "Newly developed assays for detecting genomic instability include comparative genomic hybridization using fluorescence in situ hybridization on > 20 micron-thick sections monitored by confocal laser scanning microscopy, assays for microsatellite instability, and restriction landmark genomic scanning. " 01/01/2009 - "In 213 noncancerous colorectal mucosa samples from colorectal cancer cases and 51 normal mucosa specimens of diverticulosis cases, epithelial and stromal genomic instability was analyzed with National Cancer Institute standard microsatellite markers, chromosome 17 (Chr.17) markers and tumor suppressor gene-related markers, using a combination of laser-capture microdissection and GeneScan approaches. " 07/01/2007 - "Investigation of genomic instability in paediatric Barrett's oesophagus using laser microdissection on paraffin-embedded endoscopic biopsies." 01/01/2007 - "Low-level genomic instability is a feature of papillary thyroid carcinoma: an array comparative genomic hybridization study of laser capture microdissected papillary thyroid carcinoma tumors and clonal cell lines."
5.	Chemoprevention 01/01/2007 - "One focus of chemoprevention research is the interaction of nutrients with specific molecular targets associated with the maintenance of genomic stability. " 09/20/2002 - "Impact of genomic instability in risk assessment and chemoprevention of oral premalignancies." 05/29/2003 - "This review is based on our previously published data and by searches in the Medline and PubMed databases, using the following terms as key words: "oral premalignancies", "oral leukoplakia", "tumour progression", "genomic instability", "aneuploidy", "prognosis", "head and neck cancer", and "chemoprevention". " 01/01/1997 - "Recommended chemoprevention strategies based on these mechanisms are (1) early diagnosis and treatment of genomic instability before the appearance of intraepithelial neoplasia, i.e., during the "predysplastic" or "premorphologic" phase, (2) development of multiple agents that block intralesional proliferation at steps along the "command" pathways of mitotic signal transduction and along the "execute" pathways of synthesis of daughter cell components, (3) development of nontoxic antiinflammatory agents, antioxidants, antimutagens, and proapoptotics, (4) avoidance of "clonal escape" through use of drug combinations, and (5) use of computer-assisted quantitative image analysis to assay modulation of surrogate endpoints in chemoprevention clinical trials."