keyword
MENU ▼
Read by QxMD icon Read
search

Genomic instability cancer

keyword
https://www.readbyqxmd.com/read/28096526/telomeres-in-cancer-tumour-suppression-and-genome-instability
#1
John Maciejowski, Titia de Lange
The shortening of human telomeres has two opposing effects during cancer development. On the one hand, telomere shortening can exert a tumour-suppressive effect through the proliferation arrest induced by activating the kinases ATM and ATR at unprotected chromosome ends. On the other hand, loss of telomere protection can lead to telomere crisis, which is a state of extensive genome instability that can promote cancer progression. Recent data, reviewed here, provide new evidence for the telomere tumour suppressor pathway and has revealed that telomere crisis can induce numerous cancer-relevant changes, including chromothripsis, kataegis and tetraploidization...
January 18, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28095174/medical-oncologists-experiences-in-using-genomic-testing-for-lung-and-colorectal-cancer-care
#2
Stacy W Gray, Benjamin Kim, Lynette Sholl, Angel Cronin, Aparna R Parikh, Carrie N Klabunde, Katherine L Kahn, David A Haggstrom, Nancy L Keating
PURPOSE: Genomic testing improves outcomes for many at-risk individuals and patients with cancer; however, little is known about how genomic testing for non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC) is used in clinical practice. PATIENTS AND METHODS: In 2012 to 2013, we surveyed medical oncologists who care for patients in diverse practice and health care settings across the United States about their use of guideline- and non-guideline-endorsed genetic tests...
January 17, 2017: Journal of Oncology Practice
https://www.readbyqxmd.com/read/28094570/antioxidant-anti-inflammatory-and-genomic-stability-enhancement-effects-of-zinc-l-carnosine-a-potential-cancer-chemopreventive-agent
#3
Theng Choon Ooi, Kok Meng Chan, Razinah Sharif
Cancer is one of the major causes of death worldwide, and the incidence and mortality rates of cancer are expected to rise tremendously in the near future. Despite a better understanding of cancer biology and advancement in cancer management, current strategies in cancer treatment remain costly and ineffective. Hence, instead of putting more efforts to search for new cancer cures, attention has now been shifted to the development of cancer chemopreventive agents as a preventive measure for cancer formation...
January 17, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28093453/interactions-between-microsatellite-instability-and-human-gut-colonization-by-escherichia-coli-in-colorectal-cancer
#4
Johan Gagnière, Virginie Bonnin, Anne-Sophie Jarrousse, Emilie Cardamone, Allison Agus, Nancy Uhrhammer, Pierre Sauvanet, Pierre Déchelotte, Nicolas Barnich, Richard Bonnet, Denis Pezet, Mathilde Bonnet
Recent studies suggest that colonization of colonic mucosa by pathogenic Escherichia coli (E. coli) could be involved in the development of colorectal cancer (CRC), especially through the production of genotoxins such as colibactin and/or by interfering with the DNA mismatch repair (MMR) pathway which leads to microsatellite instability (MSI). This work, performed on 88 CRC patients, revealed a significant increase in E. coli colonization in the MSI CRC phenotype. In the same way, E. coli persistence and internalization were increased IN VITRO : in MMR-deficient cells...
January 16, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28093273/identification-of-fhit-as-a-post-transcriptional-effector-of-thymidine-kinase-1-expression
#5
Daniel L Kiss, Catherine E Waters, Iman M Ouda, Joshua C Saldivar, Jenna R Karras, Zaynab A Amin, Seham Mahrous, Teresa Druck, Ralf A Bundschuh, Daniel R Schoenberg, Kay Huebner
FHIT is a genome caretaker gene that is silenced in >50% of cancers. Loss of Fhit protein expression promotes accumulation of DNA damage, affects apoptosis and epithelial-mesenchymal transition, though molecular mechanisms underlying these alterations have not been fully elucidated. Initiation of genome instability directly follows Fhit loss and the associated reduced Thymidine Kinase 1 (TK1) protein expression. The effects on TK1 of Fhit knockdown and Fhit induction in the current study confirmed the role of Fhit in regulating TK1 expression...
January 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28090586/holliday-junction-trap-shows-how-cells-use-recombination-and-a-junction-guardian-role-of-recq-helicase
#6
Jun Xia, Li-Tzu Chen, Qian Mei, Chien-Hui Ma, Jennifer A Halliday, Hsin-Yu Lin, David Magnan, John P Pribis, Devon M Fitzgerald, Holly M Hamilton, Megan Richters, Ralf B Nehring, Xi Shen, Lei Li, David Bates, P J Hastings, Christophe Herman, Makkuni Jayaram, Susan M Rosenberg
DNA repair by homologous recombination (HR) underpins cell survival and fuels genome instability, cancer, and evolution. However, the main kinds and sources of DNA damage repaired by HR in somatic cells and the roles of important HR proteins remain elusive. We present engineered proteins that trap, map, and quantify Holliday junctions (HJs), a central DNA intermediate in HR, based on catalytically deficient mutant RuvC protein of Escherichia coli. We use RuvCDefGFP (RDG) to map genomic footprints of HR at defined DNA breaks in E...
November 2016: Science Advances
https://www.readbyqxmd.com/read/28087320/poly-adp-ribose-polymerase-activity-and-inhibition-in-cancer
#7
REVIEW
Caleb Dulaney, Samuel Marcrom, Jennifer Stanley, Eddy S Yang
Genomic instability resultant from defective DNA repair mechanisms is a fundamental hallmark of cancer. The poly(ADP-ribose) polymerase (PARP) proteins 1, 2 and 3 catalyze the polymerization of poly(ADP-ribose) and covalent attachment to proteins in a phylogenetically ancient form of protein modification. PARPs play a role in base excision repair, homologous recombination, and non-homologous end joining. The discovery that loss of PARP activity had cytotoxic effects in cells deficient in homologous recombination has sparked a decade of translational research efforts that culminated in the FDA approval of an oral PARP inhibitor for clinical use in patients with ovarian cancer and defective homologous recombination...
January 10, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28079598/interobserver-agreement-in-endometrial-carcinoma-histotype-diagnosis-varies-depending-on-the-cancer-genome-atlas-tcga-based-molecular-subgroup
#8
Lien N Hoang, Mary A Kinloch, Joyce M Leo, Katherine Grondin, Cheng-Han Lee, Carol Ewanowich, Martin Köbel, Angela Cheng, Aline Talhouk, Melissa McConechy, David G Huntsman, Jessica N McAlpine, Robert A Soslow, C Blake Gilks
The Cancer Genome Atlas recently identified a genomic-based molecular classification of endometrial carcinomas, with 4 molecular categories: (1) ultramutated (polymerase epsilon [POLE] mutated), (2) hypermutated (microsatellite instability), (3) copy number abnormalities-low, and (4) copy number abnormalities-high. Two studies have since proposed models to classify endometrial carcinomas into 4 molecular subgroups, modeled after The Cancer Genome Atlas, using simplified and more clinically applicable surrogate methodologies...
February 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28076779/transcription-dynamics-prevent-rna-mediated-genomic-instability-through-srpk2-dependent-ddx23-phosphorylation
#9
Sreerama Chaitanya Sridhara, Sílvia Carvalho, Ana Rita Grosso, Lina Marcela Gallego-Paez, Maria Carmo-Fonseca, Sérgio Fernandes de Almeida
Genomic instability is frequently caused by nucleic acid structures termed R-loops that are formed during transcription. Despite their harmful potential, mechanisms that sense, signal, and suppress these structures remain elusive. Here, we report that oscillations in transcription dynamics are a major sensor of R-loops. We show that pausing of RNA polymerase II (RNA Pol II) initiates a signaling cascade whereby the serine/arginine protein kinase 2 (SRPK2) phosphorylates the DDX23 helicase, culminating in the suppression of R-loops...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28073589/mechanisms-of-oncogene-induced-genomic-instability
#10
Simona Graziano, Susana Gonzalo
Activating mutations in oncogenes promote uncontrolled proliferation and malignant transformation. Approximately 30% of human cancers carry mutations in the RAS oncogene. Paradoxically, expression of mutant constitutively active Ras protein in primary human cells results in a premature proliferation arrest known as oncogene-induced senescence (OIS). This is more commonly observed in human pre-neoplasia than in neoplastic lesions, and is considered a tumor suppressor mechanism. Senescent cells are still metabolically active but in a status of cell cycle arrest characterized by specific morphological and physiological features that distinguish them from both proliferating cells, and cells growth-arrested by other means...
November 24, 2016: Biophysical Chemistry
https://www.readbyqxmd.com/read/28073006/bcl9l-dysfunction-impairs-caspase-2-expression-permitting-aneuploidy-tolerance-in-colorectal-cancer
#11
Carlos López-García, Laurent Sansregret, Enric Domingo, Nicholas McGranahan, Sebastijan Hobor, Nicolai Juul Birkbak, Stuart Horswell, Eva Grönroos, Francesco Favero, Andrew J Rowan, Nicholas Matthews, Sharmin Begum, Benjamin Phillimore, Rebecca Burrell, Dahmane Oukrif, Bradley Spencer-Dene, Michal Kovac, Gordon Stamp, Aengus Stewart, Havard Danielsen, Marco Novelli, Ian Tomlinson, Charles Swanton
Chromosomal instability (CIN) contributes to cancer evolution, intratumor heterogeneity, and drug resistance. CIN is driven by chromosome segregation errors and a tolerance phenotype that permits the propagation of aneuploid genomes. Through genomic analysis of colorectal cancers and cell lines, we find frequent loss of heterozygosity and mutations in BCL9L in aneuploid tumors. BCL9L deficiency promoted tolerance of chromosome missegregation events, propagation of aneuploidy, and genetic heterogeneity in xenograft models likely through modulation of Wnt signaling...
January 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28069571/apc-c-dysfunction-limits-excessive-cancer-chromosomal-instability
#12
Laurent Sansregret, James O Patterson, Sally Dewhurst, Carlos López-García, André Koch, Nicholas McGranahan, William Chong Hang Chao, David J Barry, Andrew Rowan, Rachael Instrell, Stuart Horswell, Michael Way, Michael Howell, Martin R Singleton, René H Medema, Paul Nurse, Mark Petronczki, Charles Swanton
: Intercellular heterogeneity, exacerbated by chromosomal instability (CIN), fosters tumor heterogeneity and drug resistance. However, extreme CIN correlates with improved cancer outcome, suggesting that karyotypic diversity required to adapt to selection pressures might be balanced in tumors against the risk of excessive instability. Here, we used a functional genomics screen, genome editing, and pharmacologic approaches to identify CIN-survival factors in diploid cells. We find partial anaphase-promoting complex/cyclosome (APC/C) dysfunction lengthens mitosis, suppresses pharmacologically induced chromosome segregation errors, and reduces naturally occurring lagging chromosomes in cancer cell lines or following tetraploidization...
January 9, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28067867/germline-brca2-mutations-drive-prostate-cancers-with-distinct-evolutionary-trajectories
#13
Renea A Taylor, Michael Fraser, Julie Livingstone, Shadrielle Melijah G Espiritu, Heather Thorne, Vincent Huang, Winnie Lo, Yu-Jia Shiah, Takafumi N Yamaguchi, Ania Sliwinski, Sheri Horsburgh, Alice Meng, Lawrence E Heisler, Nancy Yu, Fouad Yousif, Melissa Papargiris, Mitchell G Lawrence, Lee Timms, Declan G Murphy, Mark Frydenberg, Julia F Hopkins, Damien Bolton, David Clouston, John D McPherson, Theodorus van der Kwast, Paul C Boutros, Gail P Risbridger, Robert G Bristow
Germline mutations in the BRCA2 tumour suppressor are associated with both an increased lifetime risk of developing prostate cancer (PCa) and increased risk of aggressive disease. To understand this aggression, here we profile the genomes and methylomes of localized PCa from 14 carriers of deleterious germline BRCA2 mutations (BRCA2-mutant PCa). We show that BRCA2-mutant PCa harbour increased genomic instability and a mutational profile that more closely resembles metastastic than localized disease. BRCA2-mutant PCa shows genomic and epigenomic dysregulation of the MED12L/MED12 axis, which is frequently dysregulated in metastatic castration-resistant prostate cancer (mCRPC)...
January 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28067843/maintenance-of-genome-integrity-how-mammalian-cells-orchestrate-genome-duplication-by-coordinating-replicative-and-specialized-dna-polymerases
#14
REVIEW
Ryan Barnes, Kristin Eckert
Precise duplication of the human genome is challenging due to both its size and sequence complexity. DNA polymerase errors made during replication, repair or recombination are central to creating mutations that drive cancer and aging. Here, we address the regulation of human DNA polymerases, specifically how human cells orchestrate DNA polymerases in the face of stress to complete replication and maintain genome stability. DNA polymerases of the B-family are uniquely adept at accurate genome replication, but there are numerous situations in which one or more additional DNA polymerases are required to complete genome replication...
January 6, 2017: Genes
https://www.readbyqxmd.com/read/28067794/the-tgf-%C3%AE-smad4-signaling-pathway-in-pancreatic-carcinogenesis-and-its-clinical-significance
#15
REVIEW
Sunjida Ahmed, Azore-Dee Bradshaw, Shweta Gera, M Zahidunnabi Dewan, Ruliang Xu
Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal human cancers due to its complicated genomic instability. PDAC frequently presents at an advanced stage with extensive metastasis, which portends a poor prognosis. The known risk factors associated with PDAC include advanced age, smoking, long-standing chronic pancreatitis, obesity, and diabetes. Its association with genomic and somatic mutations is the most important factor for its aggressiveness. The most common gene mutations associated with PDAC include KRas2, p16, TP53, and Smad4...
January 5, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28065761/g-quadruplexes-unfolding-by-rhau-helicase
#16
Nassima Meriem Gueddouda, Oscar Mendoza, Dennis Gomez, Anne Bourdoncle, Jean-Louis Mergny
G-quadruplexes (G4) are RNA and DNA secondary structures formed by the stacking of guanine quartets in guanine rich sequences. Quadruplex-prone motifs may be found in key genomic regions such as telomeres, ribosomal DNA, transcriptional activators and regulators or oncogene promoters. A number of proteins involved in various biological processes are able to interact with G4s. Among them, proteins dedicated to nucleic acids unwinding such as WRN, BLM, FANCJ or PIF1, can unfold G4 structures. Mutations of these helicases are linked to genome instability and to increases in cancer risks...
January 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28056863/growth-progression-and-chromosome-instability-of-neuroblastoma-a-new-scenario-of-tumorigenesis
#17
Gian Paolo Tonini
BACKGROUND: Neuroblastoma is a pediatric cancer with a low survival rate of patients with metastatic stage 4 disease. Tumor aggressiveness and progression have been associated with structural copy number variations (CNVs) that are observed in malignant cells. In contrast, localized Neuroblastomas, which are associated with a low number of structural CNVs but frequent numerical CNVs, are less aggressive, and patients have good outcomes. Finally, whole-genome and whole-exome sequencing of Neuroblastoma tissues have shown few damaging mutations in these tumors...
January 5, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28054831/lessons-learned-from-an-unstable-genomic-landscape
#18
Charles L Limoli
PURPOSE: This brief historical perspective will highlight the many accomplishments of the late William "Bill" Morgan, and how his laboratory during the mid-1990s shaped the field of genomic instability. Bill focused on the processes responsible for radiation-induced genomic instability, and while ionizing radiation was known to induce this phenomenon, the precise causes were poorly understood. Here we revisit Bill's unique approach to these problems, as he advocated the use of novel mammalian cell lines to tease apart the mechanisms responsible for destabilizing an otherwise stable nuclear genome...
January 5, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28050800/micro-rna-204-participates-in-tmprss2-erg-regulation-and-androgen-receptor-reprogramming-in-prostate-cancer
#19
Krassimira Todorova, Metodi V Metodiev, Gergana Metodieva, Milcho Mincheff, Nelson Fernández, Soren Hayrabedyan
Cancer progression is driven by genome instability incurred rearrangements such as transmembrane protease, serine 2 (TMPRSS2)/v-ets erythroblastosis virus E26 oncogene (ERG) that could possibly turn some of the tumor suppressor micro-RNAs into pro-oncogenic ones. Previously, we found dualistic miR-204 effects, acting either as a tumor suppressor or as an oncomiR in ERG fusion-dependent manner. Here, we provided further evidence for an important role of miR-204 for TMPRSS2/ERG and androgen receptor (AR) signaling modulation and fine tuning that prevents TMPRSS2/ERG overexpression in prostate cancer...
January 3, 2017: Hormones & Cancer
https://www.readbyqxmd.com/read/28049846/sir2-suppresses-replication-gaps-and-genome-instability-by-balancing-replication-between-repetitive-and-unique-sequences
#20
Eric J Foss, Uyen Lao, Emily Dalrymple, Robin L Adrianse, Taylor Loe, Antonio Bedalov
Replication gaps that persist into mitosis likely represent important threats to genome stability, but experimental identification of these gaps has proved challenging. We have developed a technique that allows us to explore the dynamics by which genome replication is completed before mitosis. Using this approach, we demonstrate that excessive allocation of replication resources to origins within repetitive regions, induced by SIR2 deletion, leads to persistent replication gaps and genome instability. Conversely, the weakening of replication origins in repetitive regions suppresses these gaps...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
keyword
keyword
104874
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"