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Mismatch repair

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https://www.readbyqxmd.com/read/28808021/kinetic-and-high-throughput-profiling-of-epigenetic-interactions-by-3d-carbene-chip-based-surface-plasmon-resonance-imaging-technology
#1
Shuai Zhao, Mo Yang, Wenfei Zhou, Baichao Zhang, Zhiqiang Cheng, Jiaxin Huang, Min Zhang, Zhiyou Wang, Rui Wang, Zhonglei Chen, Jinsong Zhu, Haitao Li
Chemical modifications on histones and DNA/RNA constitute a fundamental mechanism for epigenetic regulation. These modifications often function as docking marks to recruit or stabilize cognate "reader" proteins. So far, a platform for quantitative and high-throughput profiling of the epigenetic interactome is urgently needed but still lacking. Here, we report a 3D-carbene chip-based surface plasmon resonance imaging (SPRi) technology for this purpose. The 3D-carbene chip is suitable for immobilizing versatile biomolecules (e...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28805995/germline-pms2-and-somatic-poleexo-mutations-cause-hypermutability-of-the-leading-dna-strand-in-biallelic-mismatch-repair-deficiency-syndrome-brain-tumors
#2
Andrianova Maria, Ghati Kasturirangan Chetan, Madathan Kandi Sibin, Thomas Mckee, Doron Merkler, Rao Kvl Narasinga, Pascale Ribaux, Jean-Louis Blouin, Periklis Makrythanasis, Vladimir B Seplyarskiy, Stylianos E Antonarakis, Sergey I Nikolaev
Biallelic Mismatch Repair Deficiency (bMMRD) in tumors is frequently associated with somatic mutations in the exonuclease domains of DNA polymerases POLE or POLD1 and results to a characteristic mutational profile. In this study we describe the genetic basis of ultramutated high grade brain tumors in the context of bMMRD. We performed exome sequencing of two second-cousin patients from a large consanguineous family of Indian origin with early onset of high grade glioblastoma and astrocytoma. We identified a germline homozygous nonsense variant R802X in the PMS2 gene...
August 14, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28802267/development-of-a-transient-muts-based-hypermutation-system-for-adaptive-evolution-of-lactobacillus-casei-to-low-ph
#3
Tom J Overbeck, Dennis L Welker, Joanne E Hughes, James L Steele, Jeff R Broadbent
This study explored transient inactivation of the gene encoding the DNA mismatch repair enzyme MutS as a tool for adaptive evolution of Lactobacillus casei MutS deletion derivatives of L. casei 12A and ATCC 334 were constructed and subject to a 100-day adaptive evolution process to increase lactic acid resistance at low pH. Wild-type parental strains were also subject to this treatment. At the end of the process, the ΔmutS lesion was repaired in representative L. casei 12A and ATCC 334 ΔmutS isolates. Growth studies in broth at pH 4...
August 11, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28801307/loss-of-mutl-disrupts-chk2-dependent-cell-cycle-control-through-cdk4-6-to-promote-intrinsic-endocrine-therapy-resistance-in-primary-breast-cancer
#4
Svasti Haricharan, Nindo Punturi, Purba Singh, Kimberly R Holloway, Meenakshi Anurag, Jacob Schmelz, Cheryl Schmidt, Jonathan T Lei, Vera Suman, Kelly Hunt, John A Olson, Jeremy Hoog, Shunqiang Li, Shixia Huang, Dean P Edwards, Shyam M Kavuri, Matthew N Bainbridge, Cynthia X Ma, Matthew J Ellis
Significant endocrine therapy-resistant tumor proliferation is present in ≥20% of estrogen receptor positive (ER+) primary breast cancers and is associated with disease recurrence and death. Here, we uncover a link between intrinsic endocrine therapy resistance and dysregulation of the MutL mismatch repair complex (MLH1/3, PMS1/2), and demonstrate a direct role for MutL complex loss in resistance to all classes of endocrine therapy. We find that MutL deficiency in ER+ breast cancer abrogates Chk2-mediated inhibition of CDK4, a prerequisite for endocrine therapy responsiveness...
August 11, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28800532/cell-cycle-arrest-mediated-by-cd-induced-dna-damage-in-arabidopsis-root-tips
#5
Weina Cui, Hetong Wang, Jie Song, Xia Cao, Hilary J Rogers, Dennis Francis, Chunyun Jia, Lizong Sun, Meifang Hou, Yuesuo Yang, Peidong Tai, Wan Liu
Accumulating evidence demonstrates that the aberrant expression of cell cycle regulation and DNA repair genes can result in abnormal cell proliferation and genomic instability in eukaryotic cells under different stresses. Herein, Arabidopsis thaliana (Arabidopsis) seedlings were grown hydroponically on 0.5 × MS media containing cadmium (Cd) at 0-2.5mgL(-1) for 5d of treatment. Real time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis revealed that expression of DNA damage repair and cell cycle regulation genes, including BRCA1, MRE11, WEE1, CDKA;1 and PCNA1, showed an inverted U-shaped dose-response...
August 8, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28799290/visualizing-correlated-motion-with-hdbscan-clustering
#6
Ryan L Melvin, Jiajie Xiao, Ryan C Godwin, Kenneth S Berenhaut, Freddie R Salsbury
Correlated motion analysis provides a method for understanding communication between and dynamic similarities of biopolymer residues and domains. The typical equal-time correlation matrices - frequently visualized with pseudo-colorings or heat maps - quickly convey large regions of highly correlated motion but hide more subtle similarities of motion. Here we propose a complementary method for visualizing correlations within proteins (or general biopolymers) that quickly conveys intuition about which residues have a similar dynamic behavior...
August 11, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28797715/universal-point-of-care-testing-for-lynch-syndrome-in-patients-with-upper-tract-urothelial-carcinoma
#7
Michael J Metcalfe, Firas G Petros, Priya Rao, Maureen E Mork, Lianchun Xiao, Russell R Broaddus, Surena F Matin
BACKGROUND: Patients with Lynch syndrome (LS) are at risk for upper tract urothelial carcinoma (UTUC). We aim to identify the most reliable means of point-of-care (POC) screening for LS in UTUC patients. METHODS: From January 2013 through July 2016, 115 consecutive UTUC patients without a history of LS were universally screened during their follow-up. We evaluated patient/family history (Amsterdam criteria I [AMS1] and II [AMS2]), tumor immunohistochemistry (IHC) for mismatch repair proteins (MMRP), and microsatellite instability (MSI)...
August 7, 2017: Journal of Urology
https://www.readbyqxmd.com/read/28795426/blinded-histopathological-characterisation-of-pole-exonuclease-domain-mutant-endometrial-cancers-sheep-in-wolf-s-clothing
#8
Inge C Van Gool, Jef E H Ubachs, Ellen Stelloo, Cor D de Kroon, Jelle J Goeman, Vincent T H B M Smit, Carien L Creutzberg, Tjalling Bosse
AIMS: POLE exonuclease domain mutations identify a subset of endometrial cancer (EC) patients with an excellent prognosis. Implementation of this biomarker has been suggested to refine adjuvant treatment decisions, but the necessary sequencing is not widely performed and relatively expensive. Therefore, we aimed to identify histopathological and immunohistochemical characteristics to aid the detection of POLE-mutant ECs. METHODS AND RESULTS: Fifty-one POLE-mutant endometrioid, 67 POLE-wild-type endometrioid and 15 POLE-wild-type serous ECs were included (total N=133)...
August 10, 2017: Histopathology
https://www.readbyqxmd.com/read/28794186/hfq-links-translation-repression-to-stress-induced-mutagenesis-in-e-coli
#9
Jiandong Chen, Susan Gottesman
Mismatch repair (MMR) is a conserved mechanism exploited by cells to correct DNA replication errors both in growing cells and under nongrowing conditions. Hfq (host factor for RNA bacteriophage Qβ replication), a bacterial Lsm family RNA-binding protein, chaperones RNA-RNA interactions between regulatory small RNAs (sRNAs) and target messenger RNAs (mRNAs), leading to alterations of mRNA translation and/or stability. Hfq has been reported to post-transcriptionally repress the DNA MMR gene mutS in stationary phase, possibly limiting MMR to allow increased mutagenesis...
August 9, 2017: Genes & Development
https://www.readbyqxmd.com/read/28793134/clinical-and-genetic-implications-of-dna-mismatch-repair-deficiency-in-patients-with-pancreatic-ductal-adenocarcinoma
#10
Jordan M Cloyd, Matthew H G Katz, Huamin Wang, Amanda Cuddy, Y Nancy You
No abstract text is available yet for this article.
August 9, 2017: JAMA Surgery
https://www.readbyqxmd.com/read/28790115/msh2-loss-in-primary-prostate-cancer
#11
Liana Guedes, Emmanuel S Antonarakis, Michael T Schweizer, Nooshin Mirkheshti, Fawaz Almutairi, Jong Chul Park, Stephanie A Glavaris, Jessica L Hicks, Mario A Eisenberger, Angelo M De Marzo, Jonathan I Epstein, William B Isaacs, James R Eshleman, Colin C Pritchard, Tamara L Lotan
PURPOSE: Inactivation of mismatch repair (MMR) genes may predict sensitivity to immunotherapy in metastatic prostate cancers. We studied primary prostate tumors with MMR defects. EXPERIMENTAL DESIGN: 1133 primary prostatic adenocarcinomas and 43 prostatic small cell carcinomas (NEPC) were screened by MSH2 immunohistochemistry with confirmation by next-generation sequencing (NGS). Microsatellite instability (MSI) was assessed by PCR and NGS (mSINGS). RESULTS: Of primary adenocarcinomas and NEPC, 1...
August 8, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28781235/regulation-of-hetdna-length-during-mitotic-double-strand-break-repair-in-yeast
#12
Xiaoge Guo, Yee Fang Hum, Kevin Lehner, Sue Jinks-Robertson
Heteroduplex DNA (hetDNA) is a key molecular intermediate during the repair of mitotic double-strand breaks by homologous recombination, but its relationship to 5' end resection and/or 3' end extension is poorly understood. In the current study, we examined how perturbations in these processes affect the hetDNA profile associated with repair of a defined double-strand break (DSB) by the synthesis-dependent strand-annealing (SDSA) pathway. Loss of either the Exo1 or Sgs1 long-range resection pathway significantly shortened hetDNA, suggesting that these pathways normally collaborate during DSB repair...
August 1, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28776572/molecular-based-classification-algorithm-for-endometrial-carcinoma-categorizes-ovarian-endometrioid-carcinoma-into-prognostically-significant-groups
#13
Carlos Parra-Herran, Jordan Lerner-Ellis, Bin Xu, Sam Khalouei, Dina Bassiouny, Matthew Cesari, Nadia Ismiil, Sharon Nofech-Mozes
The Cancer Genome Atlas classification divides endometrial carcinoma in biologically distinct groups, and testing for p53, mismatch repair proteins (MMR), and polymerase ɛ (POLE) exonuclease domain mutations has been shown to predict the molecular subgroup and clinical outcome. While abnormalities in these markers have been described in ovarian endometrioid carcinoma, their role in predicting its molecular profile and prognosis is still not fully explored. Patients with ovarian endometrioid carcinomas treated surgically in a 14-year period were selected...
August 4, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28772289/association-of-mismatch-repair-mutation-with-age-at-cancer-onset-in-lynch-syndrome-implications-for-stratified-surveillance-strategies
#14
Neil A J Ryan, Julie Morris, Kate Green, Fiona Lalloo, Emma R Woodward, James Hill, Emma J Crosbie, D Gareth Evans
Importance: Lynch syndrome is caused by dominantly inherited germline mutations that predispose individuals to colorectal, endometrial, ovarian, and other cancers through inactivation of the cellular mismatch repair system. Lynch syndrome-associated cancers are amenable to surveillance strategies that may improve survival. The age at which surveillance should start is disputed. Objective: To determine whether mutated gene and type of mutation influence age at onset of Lynch syndrome-associated cancers...
August 3, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28770222/mismatch-repair-deficiency-as-a-predictive-biomarker-for-immunotherapy-efficacy
#15
REVIEW
Giulia Viale, Dario Trapani, Giuseppe Curigliano
Immunotherapy has revolutionized cancer treatment. Immune-checkpoint inhibitors, on balance, showed a favorable efficacy/toxicity profile with durable response in different cancer types. No predictive biomarker has been validated thus far to select patients who would benefit from therapy. Among the candidate predictive biomarkers, mismatch repair status of the tumor is currently one of the most promising. Indeed, tumors displaying mismatch repair deficiency or microsatellite instability showed remarkable response to immunotherapy in clinical trials...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28770104/immunoscore-in-mismatch-repair-proficient-and-deficient-colon-cancer
#16
Erkki-Ville Wirta, Toni Seppälä, Marjukka Friman, Juha Väyrynen, Maarit Ahtiainen, Hannu Kautiainen, Teijo Kuopio, Ilmo Kellokumpu, Jukka-Pekka Mecklin, Jan Böhm
The aim of this study was to investigate immune response and its prognostic significance in colon carcinomas using the previously described Immunoscore (IS). A population-based series of 779 colorectal cancers, operated on between 2000 and 2010, were classified according to tumour, node, metastasis (TNM) status, mismatch repair (MMR), and BRAF mutation status. Rectal cancer cases (n = 203) were excluded as a high proportion of these patients received preoperative neoadjuvant chemoradiotherapy. Tissue microarray (TMA) samples collected from the tumour centre and invasive front were immunostained for CD3 and CD8...
July 2017: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/28769567/thyroid-cancer-in-a-patient-with-lynch-syndrome-case-report-and-literature-review
#17
Monika Fazekas-Lavu, Andrew Parker, Allan D Spigelman, Rodney J Scott, Richard J Epstein, Michael Jensen, Katherine Samaras
Lynch syndrome describes a familial cancer syndrome comprising germline mutations in one of four DNA mismatch repair genes, MLH1, MSH2, MSH6, and PMS2 and is characterized by colorectal, endometrial, and other epithelial malignancies. Thyroid cancer is not usually considered to be part of the constellation of Lynch syndrome cancers nor have Lynch syndrome tumor gene mutations been reported in thyroid malignancies. This study reports a woman with Lynch syndrome (colonic cancer and a DNA mismatch repair mutation in the MSH2 gene) with a synchronous papillary thyroid cancer...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28767725/dna-mutation-motifs-in-the-genes-associated-with-inherited-diseases
#18
Michal Růžička, Petr Kulhánek, Lenka Radová, Andrea Čechová, Naďa Špačková, Lenka Fajkusová, Kamila Réblová
Mutations in human genes can be responsible for inherited genetic disorders and cancer. Mutations can arise due to environmental factors or spontaneously. It has been shown that certain DNA sequences are more prone to mutate. These sites are termed hotspots and exhibit a higher mutation frequency than expected by chance. In contrast, DNA sequences with lower mutation frequencies than expected by chance are termed coldspots. Mutation hotspots are usually derived from a mutation spectrum, which reflects particular population where an effect of a common ancestor plays a role...
2017: PloS One
https://www.readbyqxmd.com/read/28767666/mismatch-repair-deficient-hematopoietic-stem-cells-are-preleukemic-stem-cells
#19
Yulan Qing, Stanton L Gerson
Whereas transformation events in hematopoietic malignancies may occur at different developmental stages, the initial mutation originates in hematopoietic stem cells (HSCs), creating a preleukemic stem cell (PLSC). Subsequent mutations at either stem cell or progenitor cell levels transform the PLSC into lymphoma/leukemia initiating cells (LIC). Thymic lymphomas have been thought to develop from developing thymocytes. T cell progenitors are generated from HSCs in the bone marrow (BM), but maturation and proliferation of T cells as well as T-lymphomagenesis depends on both regulatory mechanisms and microenvironment within the thymus...
2017: PloS One
https://www.readbyqxmd.com/read/28767665/systematic-immunohistochemical-screening-for-mismatch-repair-and-ercc1-gene-expression-from-colorectal-cancers-in-china-clinicopathological-characteristics-and-effects-on-survival
#20
Pan Li, Zhitao Xiao, Todd A Braciak, Qingjian Ou, Gong Chen, Fuat S Oduncu
BACKGROUND: We performed a systematic screening of colorectal cancer (CRC) tissues to investigate whether mismatch repair (MMR) status and ERCC1 protein expression could be predictive of clinical outcomes for these patients following the recommendation of The Evaluation of Genomic Applications in Practice of Prevention (EGAPP). METHODS: The expression of four MMR genes and ERCC1 were assessed by immunohistochemistry (IHC) from cancer tissue samples of 2233 consecutive CRC patients...
2017: PloS One
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