Read by QxMD icon Read

Genomic instability

Fausto Petrelli, Sandro Barni, Giacomo Bregni, Filippo de Braud, Serena Di Cosimo
BACKGROUND: The interest in platinum salts in breast cancer (BC) therapy has been recently renewed as inhibition of DNA damage response may enhance the effects of DNA-damaging agents in BC tumors with high genomic instability. The present systematic review and meta-analysis of randomized trials were performed to assess the efficacy and safety of therapy with platinum salts in patients with locally advanced or metastatic (hereinafter advanced) BC. METHODS: We searched PubMed, EMBASE, SCOPUS, Web of Science, the Cochrane Library, and CINAHL for phase II/III clinical trials that assessed efficacy of platinum-based therapy in patients with advanced BC...
October 21, 2016: Breast Cancer Research and Treatment
Patrick H Maxwell
BACKGROUND: Accumulation of DNA damage, mutations, and chromosomal abnormalities is associated with aging in many organisms. How directly various forms of genomic instability contribute to lifespan in different aging contexts is still under active investigation. Testing whether treatments that alter lifespan change mutation rates early during lifespan could provide support for genomic instability being at least partly responsible for changes in the rates of aging. RESULTS: Rates of mutations, direct repeat recombination, or retrotransposition were measured in young cell populations from two strain backgrounds of Saccharomyces cerevisiae exposed to several growth conditions that shortened or extended yeast chronological lifespan...
October 21, 2016: BMC Genetics
Christina Gutierrez Bracamontes, Rebecca Lopez-Valdez, Ramadevi Subramani, Arunkumar Arumugam, Sushmita Nandy, Venkatesh Rajamanickam, Vignesh Ravichandran, Rajkumar Lakshmanaswamy
Early parity reduces the risk of breast cancer in women while nulliparity and late parity increase the risk of breast cancer. In order to translate this protection to women where early pregnancy is not feasible, much work has focused on understanding how parity confers protection against breast cancer, the molecular mechanisms by which this occurs is still not well understood. Healthy parous and nulliparous women were recruited for this study. We assessed serum protein profiles of early parous, late parous, and nulliparous women using the Phospho Explorer antibody array...
October 19, 2016: Oncotarget
Rui Zhang, Chang Liu, Yahan Niu, Ying Jing, Haiyang Zhang, Jin Wang, Jie Yang, Ke Zen, Junfeng Zhang, Chen-Yu Zhang, Donghai Li
The DNA damage response is critical for maintaining genome integrity and preventing damage to DNA due to endogenous and exogenous insults. Mitomycin C (MMC), a potent DNA cross-linker, is used as a chemotherapeutic agent because it causes DNA inter-strand cross-links (DNA ICLs) in cancer cells. While many microRNAs, which may serve as oncogenes or tumor suppressors, are grossly dysregulated in human cancers, little is known about their roles in MMC-treated lung cancer. Here, we report that miR-128-3p can attenuate repair of DNA ICLs by targeting SPTAN1 (αII Sp), resulting in cell cycle arrest and promoting chromosomal aberrations in lung cancer cells treated with MMC...
September 28, 2016: Oncotarget
Ya-Qin Tan, Jing Zhang, Gang Zhou
Macroautophagy/autophagy is a conserved lysosomal degradation process essential for cell physiology and human health. By regulating apoptosis, inflammation, pathogen clearance, immune response and other cellular processes, autophagy acts as a modulator of pathogenesis and is a potential therapeutic target in diverse diseases. With regard to oral disease, autophagy can be problematic either when it is activated or impaired, because this process is involved in diverse functions, depending on the specific disease and its level of progression...
October 20, 2016: Autophagy
Mark O'Driscoll
Accurate and efficient replication of the human genome occurs in the context of an array of constitutional barriers including regional topological constraints imposed by chromatin architecture and processes such as transcription, catenation of the helical polymer and spontaneously generated DNA lesions including base modifications and strand breaks. DNA replication is fundamentally important for tissue development and homeostasis; differentiation programmes are intimately linked with stem cell division. Unsurprisingly, impairments of the DNA replication machinery can have catastrophic consequences for genome stability and cell division...
October 18, 2016: Journal of Pathology
Anya Alayev, Rachel S Salamon, Subrata Manna, Naomi S Schwartz, Adi Y Berman, Marina K Holz
Homologous recombination (HR) is a conserved process that maintains genome stability and cell survival by repairing DNA double-strand breaks (DSBs). The RAD51-related family of proteins is involved in repair of DSBs; consequently, deregulation of RAD51 causes chromosomal rearrangements and stimulates tumorigenesis. RAD51C has been identified as a potential tumor suppressor and a breast and ovarian cancer susceptibility gene. Recent studies have also implicated estrogen as a DNA-damaging agent that causes DSBs...
October 18, 2016: Cell Cycle
Qing Yang, Yingqiu Xie, Lixia Miao
Cancers induced by gene mutation, deletion, and genome instability might be related to aging. With similar pathways of aging but distinct functions, senescence at the cellular level is an irreversible arrest of cell cycle. Senescence has long been believed as a barrier to restrict tumor expansion. However, more and more evidence has been shown that senescence inducers regulate epithelial-mesenchymal transition, stem cell self-renewal, inflammatory response, crosstalk with the oncogenic bypass signaling, and conversion of oncogene to tumor suppressor...
October 18, 2016: Cancer Investigation
Daniel Nava Rodrigues, Gunther Boysen, Semini Sumanasuriya, George Seed, Angelo M De Marzo, Johann de Bono
Prostate cancer (PCa) is a clinically heterogeneous disease and current treatment strategies are based largely on anatomical and pathological parameters. In the recent past, several DNA sequencing studies of primary and advanced PCa have revealed recurrent patterns of genomic aberrations that expose mechanisms of resistance to available therapies and potential new drug targets. Suppression of androgen receptor (AR) signalling is the cornerstone of advanced prostate cancer treatment. Genomic aberrations of the androgen receptor or alternative splicing of its mRNA are increasingly recognized as biomarkers of resistance to AR-targeted therapy such as abiraterone or enzalutamide...
October 18, 2016: Journal of Pathology
Nathan D Montgomery, Wilborn B Coward, Steven Johnson, Ji Yuan, Margaret L Gulley, Stephanie P Mathews, Kathleen Kaiser-Rogers, Kathleen W Rao, Warren G Sanger, Jennifer N Sanmann, Yuri Fedoriw
Classical Hodgkin lymphoma (CHL) is morphologically characterized by scattered malignant Hodgkin/Reed-Sternberg (HRS) cells that are far outnumbered by surrounding reactive hematolymphoid cells. Approximately half of all cases of CHL are associated with infection by Epstein-Barr virus (EBV), an oncogenic herpesvirus that expresses a number of proteins thought to contribute to transformation. While a small number of published studies have attempted to identify recurrent cytogenetic abnormalities in CHL, no large case series have explored karyotypic differences between EBV-positive and EBV-negative tumors...
September 2016: Cancer Genetics
Nicole E McNeil, Hesed M Padilla-Nash, Floryne O Buishand, Yue Hue, Thomas Ried
Human colorectal carcinomas are defined by a non-random distribution of genomic imbalances that are characteristic for this disease. Often, these imbalances affect entire chromosomes. Understanding the role of these aneuploidies for carcinogenesis is of utmost importance. Currently, established transgenic mice do not recapitulate the pathognonomic genome aberration profile of human colorectal carcinomas. We have developed a novel model based on the spontaneous transformation of murine colon epithelial cells...
October 17, 2016: Genes, Chromosomes & Cancer
Joo Hwa Lee, Nam Jin Yoo, Min Sung Kim, Sug Hyung Lee
Alterations of genes involved in histone modification are common in cancers. A histone demethylase-encoding gene PHF2 is considered a putative tumor suppressor gene (TSG). PHF2 is essential for p53-mediated TSG functions such as chemotherapy-mediated cancer cell killing. However, inactivating mutations of PHF2 that could inactivate its functions are not reported in cancers. In a genome database, we observed that the PHF2 gene possessed mononucleotide repeats, which could be mutated in cancers with high microsatellite instability (MSI-H)...
October 15, 2016: Pathology Oncology Research: POR
Otília Menyhárt, Hajnalka Harami-Papp, Saraswati Sukumar, Reinhold Schäfer, Luca Magnani, Oriol de Barrios, Balázs Győrffy
The hallmarks of cancer capture the most essential phenotypic characteristics of malignant transformation and progression. Although numerous factors involved in this multi-step process are still unknown to date, an ever-increasing number of mutated/altered candidate genes are being identified within large-scale cancer genomic projects. Therefore, investigators need to be aware of available and appropriate techniques capable of determining characteristic features of each hallmark. We review the methods tailored to experimental cancer researchers to evaluate cell proliferation, programmed cell death, replicative immortality, induction of angiogenesis, invasion and metastasis, genome instability, and reprogramming of energy metabolism...
October 11, 2016: Biochimica et Biophysica Acta
Yan Sun, Ping Ji, Tao Chen, Xinhui Zhou, Da Yang, Yuhong Guo, Yuexin Liu, Limei Hu, Dianren Xia, Yanxue Liu, Asha S Multani, Ilya Shmulevich, Raju Kucherlapati, Scott Kopetz, Anil K Sood, Stanley R Hamilton, Baocun Sun, Wei Zhang
The gene encoding Migration and Invasion Inhibitory Protein (MIIP), located on 1p36.22, is a potential tumour suppressor gene in glioma. In this study, we aimed to explore the role and mechanism of action of MIIP in colorectal cancer (CRC). MIIP protein expression gradually decreased along the colorectal adenoma-carcinoma sequence and was negatively correlated with lymph node and distant metastasis in 526 colorectal tissue samples (P<0.05 for all). Analysis of The Cancer Genome Atlas (TCGA) data showed that decreased MIIP expression was significantly associated with MIIP hemizygous deletion (P=0...
October 14, 2016: Journal of Pathology
Mae L Woods, Chris P Barnes
DNA double-strand breaks are lesions that form during metabolism, DNA replication and exposure to mutagens. When a double-strand break occurs one of a number of repair mechanisms is recruited, all of which have differing propensities for mutational events. Despite DNA repair being of crucial importance, the relative contribution of these mechanisms and their regulatory interactions remain to be fully elucidated. Understanding these mutational processes will have a profound impact on our knowledge of genomic instability, with implications across health, disease and evolution...
October 2016: PLoS Computational Biology
Sabrina F Mansilla, Agustina P Bertolin, Valérie Bergoglio, Marie-Jeanne Pillaire, Marina A González Besteiro, Carlos Luzzani, Santiago G Miriuka, Christophe Cazaux, Jean-Sébastien Hoffmann, Vanesa Gottifredi
The levels of the cyclin-dependent kinase (CDK) inhibitor p21 are low in S phase and insufficient to inhibit CDKs. We show here that endogenous p21, instead of being residual, it is functional and necessary to preserve the genomic stability of unstressed cells. p21depletion slows down nascent DNA elongation, triggers permanent replication defects and promotes the instability of hard-to-replicate genomic regions, namely common fragile sites (CFS). The p21's PCNA interacting region (PIR), and not its CDK binding domain, is needed to prevent the replication defects and the genomic instability caused by p21 depletion...
October 14, 2016: ELife
Jessica Woodward, Gillian C Taylor, Dinesh C Soares, Shelagh Boyle, Daoud Sie, David Read, Keerthi Chathoth, Milica Vukovic, Nuria Tarrats, David Jamieson, Kirsteen J Campbell, Karen Blyth, Juan Carlos Acosta, Bauke Ylstra, Mark J Arends, Kamil R Kranc, Andrew P Jackson, Wendy A Bickmore, Andrew J Wood
Chromosomal instability is a hallmark of cancer, but mitotic regulators are rarely mutated in tumors. Mutations in the condensin complexes, which restructure chromosomes to facilitate segregation during mitosis, are significantly enriched in cancer genomes, but experimental evidence implicating condensin dysfunction in tumorigenesis is lacking. We report that mice inheriting missense mutations in a condensin II subunit (Caph2(nes)) develop T-cell lymphoma. Before tumors develop, we found that the same Caph2 mutation impairs ploidy maintenance to a different extent in different hematopoietic cell types, with ploidy most severely perturbed at the CD4(+)CD8(+) T-cell stage from which tumors initiate...
October 13, 2016: Genes & Development
Jianing Zhong, Xianfeng Li, Wanshi Cai, Yan Wang, Shanshan Dong, Jie Yang, Jian'an Zhang, Nana Wu, Yuanyuan Li, Fengbiao Mao, Cheng Zeng, Jinyu Wu, Xingzhi Xu, Zhong Sheng Sun
The Ten Eleven Translocation 1 (TET1) protein is a DNA demethylase that regulates gene expression through altering statue of DNA methylation. However, recent studies have demonstrated that TET1 could modulate transcriptional expression independent of its DNA demethylation activity; yet, the detailed mechanisms underlying TET1's role in such transcriptional regulation remain not well understood. Here, we uncovered that Tet1 formed a chromatin complex with histone acetyltransferase Mof and scaffold protein Sin3a in mouse embryonic stem cells by integrative genomic analysis using publicly available ChIP-seq data sets and a series of in vitro biochemical studies in human cell lines...
October 12, 2016: Nucleic Acids Research
Songmi Kim, Chun-Sung Cho, Kyudong Han, Jungnam Lee
Transposable elements are one of major sources to cause genomic instability through various mechanisms including de novo insertion, insertion-mediated genomic deletion, and recombination-associated genomic deletion. Among them is Alu element which is the most abundant element, composing ~10% of the human genome. The element emerged in the primate genome 65 million years ago and has since propagated successfully in the human and non-human primate genomes. Alu element is a non-autonomous retrotransposon and therefore retrotransposed using L1-enzyme machinery...
September 2016: Genomics & Informatics
Emily Swanzey, Matthias Stadtfeld
Genomic imprinting results in the monoallelic expression of genes that encode important regulators of growth and proliferation. Dysregulation of imprinted genes, such as those within the Dlk1-Dio3 locus, is associated with developmental syndromes and specific diseases. Our ability to interrogate causes of imprinting instability has been hindered by the absence of suitable model systems. Here, we describe a Dlk1 knockin reporter mouse that enables single-cell visualization of allele-specific expression and prospective isolation of cells, simultaneously...
October 11, 2016: Development
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"