846,997 results match your criteria Mutation Research - Reviews in Mutation Research [Journal]


[Genetic profiling in the diagnosis of hereditary prostate cancer: Where do we stand?]

Aktuelle Urol 2018 Dec 6;49(6):525-529. Epub 2018 Dec 6.

Johannes Gutenberg Universitat Universitatsmedizin, Klinik und Poliklinik für Urologie und Kinderurologie, Mainz.

Prostate cancer has a heterogeneous genetic profile compared with other tumour entities. Accordingly, there are also various mutations that increase the risk of prostate cancer. Some genetic variants only have a mild impact, whereas other gene mutations (BRCA1 /2; HOXB13) may increase the risk significantly. Read More

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December 2018
5 Reads

A PALB2 truncating mutation: Implication in cancer prevention and therapy of Hereditary Breast and Ovarian Cancer.

Breast 2018 Nov 29;43:91-96. Epub 2018 Nov 29.

Cancer Genetics Group, Institute of Genetics and Molecular Biology (UVa-CSIC), Sanz y Forés 3, 47003 Valladolid, Spain. Electronic address:

Explaining genetic predisposition in Hereditary Breast and Ovarian Cancer (HBOC) families without BRCA mutations is crucial. Germline PALB2 inactivating mutations were associated with an increased risk of HBOC due to its role in DNA repair through cooperation with BRCA proteins. The prevalence and penetrance of PALB2 mutations in Spanish HBOC patients remains unexplained. Read More

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November 2018
2 Reads

Loss of enzyme activity in mutated B4GALNT1 gene products in patients with hereditary spastic paraplegia results in relatively mild neurological disorders: Similarity with phenotypes of B4galnt1 knockout mice.

Neuroscience 2018 Dec 3. Epub 2018 Dec 3.

Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai 487-8501, Japan; Department of Biochemistry II, Nagoya University Graduate School of Medicine, Nagoya 466-0065, Japan. Electronic address:

B4GALNT1 is an enzyme essential for the synthesis of complex gangliosides, whose absence leads to progressive neurodegeneration with aging in mice. Recently, eleven cases of hereditary spastic paraplegia with mutation in the coding region of B4GALNT1 were reported. However, changes in the enzymatic activity of their products have never been studied. Read More

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December 2018
2 Reads

EGFR-mutant SCLC exhibits heterogeneous phenotypes and resistance to common antineoplastic drugs.

J Thorac Oncol 2018 Dec 3. Epub 2018 Dec 3.

Department of Internal Medicine, National Taiwan University Hospital, Taiwan. Electronic address:

Introduction: Approximately 5% of patients with EGFR-activating mutations acquire EGFR-TKIs resistance through SCLC transformation. However, the reason for the poor outcome and the molecular basis of EGFR-mutant SCLC that has transformed from adenocarcinoma remain unclear.

Methods: In this study, we established 2 EGFR-mutant SCLC cell lines from lung adenocarcinoma patients after failed EGFR-TKI treatment to investigate their molecular basis and potential therapeutic strategies in the hope of improving patient outcome. Read More

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December 2018
3 Reads

The unique spatial-temporal treatment failure patterns of adjuvant gefitinib therapy: A post-hoc analysis of the ADJUVANT trial (CTONG 1104).

J Thorac Oncol 2018 Dec 3. Epub 2018 Dec 3.

Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China. Electronic address:

Introduction: Adjuvant gefitinib therapy prolonged disease-free survival (DFS) in patients with resected early-stage epidermal growth factor receptor (EGFR)-mutation positive non-small cell lung cancer (NSCLC) in the ADJUVANT study (CTONG 1104). However, treatment failure patterns after gefitinib therapy are less well characterized.

Methods: Overall, 222 stage N1-N2, EGFR-mutant NSCLC patients received gefitinib or vinorelbine plus cisplatin (VP) treatment. Read More

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December 2018
3 Reads

Loss of K607 and E877 interaction is a key reason for JAK2 K607N mutation caused acute myeloid leukemia.

Int J Biol Macromol 2018 Dec 3. Epub 2018 Dec 3.

Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China; Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. Electronic address:

Oncogenic activation of tyrosine kinase signaling pathway is recurrent in human leukemia. The acquired Janus kinase 2 (JAK2) K607N somatic mutation was detected in about 6.8% of acute myeloid leukemia (AML) patients. Read More

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December 2018
2 Reads
2.858 Impact Factor

Study of tau pathology in male rTg4510 mice fed with a curcumin derivative Shiga-Y5.

PLoS One 2018 6;13(12):e0208440. Epub 2018 Dec 6.

Molecular Neuroscience Research Center, Shiga University of Medical Science, Otsu, Japan.

Intracellular inclusions of aggregated tau appear in neurons and glial cells in a range of neurodegenerative diseases known as tauopathies. Inhibition of pathological changes in tau is a therapeutic target for tauopathy. We recently synthesized a novel curcumin derivative, named Shiga-Y5, and showed that Shiga-Y5 inhibited cognitive impairment and amyloid deposition in a mouse model of Alzheimer's disease. Read More

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December 2018
2 Reads

Whole genome variant association across 100 dogs identifies a frame shift mutation in DISHEVELLED 2 which contributes to Robinow-like syndrome in Bulldogs and related screw tail dog breeds.

PLoS Genet 2018 Dec 6;14(12):e1007850. Epub 2018 Dec 6.

Department of Population Health and Reproduction, School of Veterinary Medicine, University of California Davis, Davis, CA, United States of America.

Domestic dog breeds exhibit remarkable morphological variations that result from centuries of artificial selection and breeding. Identifying the genetic changes that contribute to these variations could provide critical insights into the molecular basis of tissue and organismal morphogenesis. Bulldogs, French Bulldogs and Boston Terriers share many morphological and disease-predisposition traits, including brachycephalic skull morphology, widely set eyes and short stature. Read More

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December 2018
5 Reads

Unexplained cytopenias in an adolescent? You GATA think about it.

J Assoc Genet Technol 2018 ;44(4):135-136

Department of Pathology and Laboratory Medicine, University of Vermont Medical Center, Burlington, VT.

Objectives: The GATA family of DNA binding proteins consists of six different transcription factors (GATA1-6), each with a diverse biologic function. The transcription factors GATA1-3 function primarily to orchestrate hematopoiesis; however, they have roles in non-hematopoietic cells as well. Much of our current knowledge of the GATA transcription factors has come through observation of disease states with known GATA mutations. Read More

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January 2018

In vivo monitoring of intracellular Ca dynamics in the pancreatic β-cells of zebrafish embryos.

Islets 2018 Dec 6:1-18. Epub 2018 Dec 6.

a Institute of Molecular Biology/CMBI , University of Innsbruck , Innsbruck , Austria.

Assessing the response of pancreatic islet cells to glucose stimulation is important for understanding β-cell function. Zebrafish are a promising model for studies of metabolism in general, including stimulus-secretion coupling in the pancreas. We used transgenic zebrafish embryos expressing a genetically-encoded Ca sensor in pancreatic β-cells to monitor a key step in glucose induced insulin secretion; the elevations of intracellular [Ca]. Read More

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December 2018
1 Read

Target engagement and binding mode of an anti-tuberculosis drug to its bacterial target deciphered in whole living cells by NMR.

Biochemistry 2018 Dec 6. Epub 2018 Dec 6.

Detailed information on hit-target interaction is very valuable for drug discovery efforts and indispensable for rational hit to lead optimization. We developed a new approach combining NMR in whole-cells (in-cell NMR) and docking to characterize hit-target interaction at the atomic level. By using in-cell NMR, we validated target engagement of the anti-tuberculosis imidazopyridine amide (IPA) series with the subunit b of the cytochrome bc1:aa3, the major respiratory terminal oxidase in mycobacteria. Read More

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December 2018

Overcoming T790M mutant small cell lung cancer with the third-generation EGFR-TKI osimertinib.

Thorac Cancer 2018 Dec 6. Epub 2018 Dec 6.

Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

A large number of EGFR mutant non-small cell lung cancer patients primordially benefit from first-line treatment with first-generation EGFR-tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib. However, multiple acquired resistance mechanisms have been described that limit the clinical efficacy of first-generation EGFR-TKIs. Herein, we report a rare case of lung adenocarcinoma harboring an EGFR exon 19-deletion mutation before the administration of target therapy. Read More

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December 2018

Universal screening for Lynch Syndrome in a large consecutive cohort of Chinese colorectal cancer patients: high prevalence and unique molecular features.

Int J Cancer 2018 Dec 6. Epub 2018 Dec 6.

Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.

The prevalence of Lynch syndrome (LS) varies significantly in different populations, suggesting that ethnic features might play an important role. We enrolled 3330 consecutive Chinese patients who had surgical resection for newly diagnosed colorectal cancer. Universal screening for LS was implemented, including immunohistochemistry for mismatch repair (MMR) proteins, BRAF mutation test and germline sequencing. Read More

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December 2018
2 Reads
5.085 Impact Factor

Possible cold-adaptation for the fungal kinesin in compensation for thermal stability acquired by single amino acid substitution.

J Biochem 2018 Dec 5. Epub 2018 Dec 5.

Department of Biosciences, College of Humanities and Sciences, Nihon University, 3-25-40 Sakurajosui, Setagaya-ku, Tokyo, Japan.

The amino acid sequence of the motor domain of AnKinA, kinesin-1 from Aspergillus nidulans, growing optimally at 37°C, was compared with that of SbKin1, kinesin-1 from the snow mold Sclerotinia borealis. For cold-adaptation, some enzymes are thought to exhibit augmented protein structure flexibility, acquired most effectively by substituting a glycine residue for another amino acid residue. By the comparison described above, two glycine residues proximal to tightly-bound ADP were identified in the SbKin1 motor domain, of which the corresponding residues of AnKinA were non-glycine ones (P60 and S323). Read More

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December 2018
1 Read

Risk-Reducing Mastectomy in BRCA1 and BRCA2 Mutation Carriers: A Complex Discussion.

Authors:
Susan M Domchek

JAMA 2018 Dec 6. Epub 2018 Dec 6.

Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania, Philadelphia.

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December 2018

Hereditary Spastic Paraplegia: gain-of-function mechanisms revealed by new transgenic mouse.

Hum Mol Genet 2018 Dec 6. Epub 2018 Dec 6.

Department of Neurobiology and Anatomy.

Mutations of the SPAST gene, which encodes the microtubule-severing protein spastin, are the most common cause of Hereditary Spastic Paraplegia. Haploinsufficiency is the prevalent opinion as to the mechanism of the disease, but gain-of-function toxicity of the mutant proteins is another possibility. Here, we report a new transgenic mouse (termed SPASTC448Y mouse) that is not haploinsufficient but expresses human spastin bearing the HSP pathogenic C448Y mutation. Read More

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December 2018

Protein-protein interaction sites prediction by ensemble random forests with synthetic minority oversampling technique.

Bioinformatics 2018 Dec 5. Epub 2018 Dec 5.

Bioinformatics and Mathematical Biosciences Lab, Department of Agronomy, Horticulture and Plant Science, South Dakota State University, Brookings, SD, USA.

Motivation: The prediction of protein-protein interaction (PPI) sites is a key to mutation design, catalytic reaction, and the reconstruction of PPI networks. It is a challenging task considering the significant abundant sequences and the imbalance issue in samples.

Results: A new ensemble learning based method, EL-SMURF, was proposed for PPI sites prediction in this study. Read More

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December 2018
1 Read

In silico error correction improves cfDNA mutation calling.

Bioinformatics 2018 Dec 6. Epub 2018 Dec 6.

Medical Research Council Manchester Single Cell Research Centre, University of Manchester, Alderley Park, Manchester, UK.

Motivation: Circulating-free DNA (cfDNA) profiling by sequencing is an important minimally invasive protocol for monitoring the mutation profile of solid tumours in cancer patients. Since the concentration of available cfDNA is limited, sample library generation relies on multiple rounds of PCR amplification, during which the accumulation of errors results in reduced sensitivity and lower accuracy.

Results: We present PCR Error Correction (PEC), an algorithm to identify and correct errors in short read sequencing data. Read More

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December 2018
1 Read

Cholangiolocellular Carcinoma With "Ductal Plate Malformation" Pattern may be Characterized by ARID1A Genetic Alterations.

Am J Surg Pathol 2018 Dec 4. Epub 2018 Dec 4.

Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa.

Cholangiolocellular carcinoma (CLC) is a unique subtype of primary liver carcinoma, which sometimes coexists with hepatocellular carcinoma (HCC), cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma (cHCC-CCA). "Ductal plate malformation" (DPM)-pattern of primary liver carcinoma, which resembles biliary lesions in Caroli disease and von Meyenburg complex, is sometimes associated with CLC. We examined genetic alterations of hTERT promoter (hTERT), IDH1 or 2 (IDH1/2), KRAS, ARID1A, PBRM1, ARID2, BAP1, p53 and their association with histologic features such as proportion of CLC and DPM-pattern in 77 patients with primary liver carcinoma diagnosed as cHCC-CCA or CLC. Read More

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December 2018
1 Read

Engineered Heart Slice Model of Arrhythmogenic Cardiomyopathy using Plakophilin-2 Mutant Myocytes.

Tissue Eng Part A 2018 Dec 6. Epub 2018 Dec 6.

Johns Hopkins University School of Medicine, Biomedical Engineering, Baltimore, Maryland, United States ;

Arrhythmogenic cardiomyopathy (AC), a cause of sudden cardiac death among young and otherwise healthy individuals, is a heritable disease that can be modeled in vitro using patient-specific cardiac myocytes (CMs) from induced pluripotent stem cells. An understanding of underlying disease mechanisms, particularly in the early concealed stages, could lead to new diagnosis and treatment strategies. However, multicellular syncytial models are needed to understand how genetically-encoded mutations of the desmosomes that interconnect cells lead to aberrant electrical conduction and arrhythmias. Read More

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December 2018

Epidermolytic ichthyosis due to a de novo missense mutation c.1307T> C; p.Leu436Pro in KRT10.

J Dtsch Dermatol Ges 2018 Dec 6. Epub 2018 Dec 6.

Department of Dermatology, Carl Gustav Carus University Medical Center, Dresden Technical University, Dresden, Germany.

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December 2018
1 Read

TDP-43 accelerates deadenylation of target mRNAs by recruiting Caf1 deadenylase.

FEBS Lett 2018 Dec 6. Epub 2018 Dec 6.

Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, 467-8603, Japan.

TAR DNA-binding protein 43 (TDP-43) is an RNA-binding protein, whose loss-of-function mutation causes amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Recent studies demonstrated that TDP-43 binds to the 3' UTR of target mRNAs to promote mRNA instability. Here, we show that TDP-43 recruits Caf1 deadenylase to mRNA targets and accelerates their deadenylation. Read More

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December 2018

Advanced Non Small Cell Lung Cancer with activating Epidermal Growth Factor Receptor mutation: First line treatment and beyond.

Rev Recent Clin Trials 2018 Dec 5. Epub 2018 Dec 5.

Division of Medical Oncology, AORN Giuseppe Moscati, Avellino. Italy.

Background: Lung cancer is the leading cause of cancer mortality, being responsible for more than 1.6 million deaths each year worldwide and non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancers; moreover, 10 to 15% of all NSCLCs harbors EGFR (epidermal growth factor receptor) activating mutations, being suitable for EGFR-Tyrosine Kinase Inhibitors (TKI) molecular targeted therapy. However, EGFR+ NSCLCs gain acquired resistance to these agents, representing one of the key challenges for modern precision oncology. Read More

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December 2018

Application of the Co-Agonist Concerted Transition Model to Analysis of GABAA Receptor Properties.

Curr Neuropharmacol 2018 Dec 5. Epub 2018 Dec 5.

Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO. United States.

The co-agonist concerted transition model is a simple and practical solution to analyzing various aspects of GABAA receptor function. Several model-based predictions have been verified experimentally in previous reports. We review here the practical implications of the model and demonstrate how it enables simplification of the experimental procedure and data analysis to characterize the effects of mutations or properties of novel ligands. Read More

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December 2018

Co-occurrence of V1016I and F1534C mutations in the voltage-gated sodium channel and resistance to pyrethroids in Aedes aegypti (L.) from the Colombian Caribbean region.

Pest Manag Sci 2018 Dec 5. Epub 2018 Dec 5.

Universidad Autonoma de Nuevo Leon, Facultad de Ciencias Biologicas, Av. Universidad s/n Cd. Universitaria, San Nicolás de los Garza, NL, 66455, Mexico.

Background: Knockdown resistance is conferred primarily by non-synonymous mutations that reduce pyrethroids binding to voltage-gated sodium channels. In 2014, kdr mutation V1016I in Aedes aegypti populations resistant to pyrethroids was reported for the first time in Colombiα, in 2016 another kdr mutation, F1534C and in 2018 the mutation V419L. Nine populations of A. Read More

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December 2018
1 Read

ERBB2 mutation frequency in lobular breast cancer with pleomorphic histology or high-risk characteristics by molecular expression profiling.

Genes Chromosomes Cancer 2018 Dec 5. Epub 2018 Dec 5.

Institute of Pathology, Hannover Medical School, Hannover, Germany.

HER2-positive breast cancer is defined by amplification or overexpression of the HER2/ERBB2 oncogene and accounts for about 15% of breast cancer (BC) cases. Somatic mutation of ERBB2 is an alternative mechanism, by which activation of HER2 signaling can occur. ERBB2 mutation has been associated with invasive lobular breast cancer (ILBC). Read More

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December 2018
1 Read

Phase I/II study of dasatinib and exploratory genomic analysis in relapsed or refractory non-Hodgkin lymphoma.

Br J Haematol 2018 Dec 5. Epub 2018 Dec 5.

Division of Oncology & Hematology, University of Nebraska Medical Center, Omaha, NE, USA.

Relapsed or refractory non-Hodgkin lymphomas (NHLs) often carry poor prognosis and pose management challenges. We evaluated the safety and efficacy of dasatinib, a broad-spectrum multi-kinase inhibitor in relapsed/refractory NHL with correlative genomic analysis in a Phase I/II trial. The study included 33 patients with various sub-types of NHL who had received at least one prior therapy. Read More

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December 2018
5 Reads

Genetic profiling of basal cell carcinomas detects postzygotic mosaicism in basal cell naevus syndrome.

Br J Dermatol 2018 Dec 5. Epub 2018 Dec 5.

Department of Dermatology, Maastricht University Medical Center, Maastricht, the Netherlands.

Basal cell naevus syndrome (BCNS) is associated with germline mutations in the PTCH1 gene. Postzygotic mosaicism can also cause BCNS. Here we describe two patients, one with multiple basal cell carcinomas (BCCs) and one with clinical BCNS, who had no PTCH1 mutation in DNA extracted from blood. Read More

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December 2018
1 Read

Mitochondrial Electron Transport Chain Complex Dysfunction in MeCP2 Knock-Down Astrocytes: Protective Effects of Quercetin Hydrate.

J Mol Neurosci 2018 Dec 6. Epub 2018 Dec 6.

Division of Neurobiology, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India.

Astrocytes play the central role in CNS metabolism to support neuronal functions. Mehyl-CpG-binding protein 2 (MeCP2) is the global transcription factor with differential expression in neuronal and non-neuronal cells. MeCP2 mutation and downstream detrimental effects have been reported in astrocytes also in MeCP2-associated neurodevelopmental disorder-Rett syndrome. Read More

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December 2018
5 Reads

Recombinant Human FSH Treatment Outcomes in Five Boys With Severe Congenital Hypogonadotropic Hypogonadism.

J Endocr Soc 2018 Dec 15;2(12):1345-1356. Epub 2018 Oct 15.

University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Context: Recombinant human FSH (r-hFSH), given to prepubertal boys with hypogonadotropic hypogonadism (HH), may induce Sertoli cell proliferation and thereby increase sperm-producing capacity later in life.

Objective: To evaluate the effects of r-hFSH, human chorionic gonadotropin (hCG), and testosterone (T) in such patients.

Design And Setting: Retrospective review in three tertiary centers in Finland between 2006 and 2016. Read More

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December 2018

Risk Model in Women with Ovarian Cancer Without Mutations.

Open Med (Wars) 2018 25;13:565-574. Epub 2018 Nov 25.

Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University, Szczecin, Poland.

Ovarian cancer is characterised by the greatest mortality among all tumors of the reproductive tract. This study included 246 patients which consisted of 136 women with ovarian cancer without genetic mutation and 110 women with benign ovarian cysts. We created two mathematical logic models containing positive and negative risk factors of ovarian cancer such as: age at last menstruation cycle, patient age, OC, HRT, smoking, education status, and alcohol consumption. Read More

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November 2018

Zinc Blockade of SOS Response Inhibits Horizontal Transfer of Antibiotic Resistance Genes in Enteric Bacteria.

Front Cell Infect Microbiol 2018 21;8:410. Epub 2018 Nov 21.

Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, United States.

The SOS response is a conserved response to DNA damage that is found in Gram-negative and Gram-positive bacteria. When DNA damage is sustained and severe, activation of error-prone DNA polymerases can induce a higher mutation rate than is normally observed, which is called the SOS mutator phenotype or hypermutation. We previously showed that zinc blocked the hypermutation response induced by quinolone antibiotics and mitomycin C in and . Read More

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November 2018
1 Read

Risdiplam distributes and increases SMN protein in both the central nervous system and peripheral organs.

Pharmacol Res Perspect 2018 Dec 29;6(6):e00447. Epub 2018 Nov 29.

Roche Pharma Research and Early Development Roche Innovation Center Basel Switzerland.

Spinal muscular atrophy (SMA) is a rare, inherited neuromuscular disease caused by deletion and/or mutation of the Survival of Motor Neuron 1 ( gene. A second gene, , produces low levels of functional SMN protein that are insufficient to fully compensate for the lack of . Risdiplam (RG7916; RO7034067) is an orally administered, small-molecule pre-mRNA splicing modifier that distributes into the central nervous system (CNS) and peripheral tissues. Read More

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December 2018
1 Read

Breaking point: the genesis and impact of structural variation in tumours.

F1000Res 2018 19;7. Epub 2018 Nov 19.

MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, The University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH42XU, UK.

Somatic structural variants undoubtedly play important roles in driving tumourigenesis. This is evident despite the substantial technical challenges that remain in accurately detecting structural variants and their breakpoints in tumours and in spite of our incomplete understanding of the impact of structural variants on cellular function. Developments in these areas of research contribute to the ongoing discovery of structural variation with a clear impact on the evolution of the tumour and on the clinical importance to the patient. Read More

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November 2018

Change over time of the mutagenicity in the lungs of delta transgenic mice by extract of airborne particles collected from ambient air in the Tokyo metropolitan area.

Genes Environ 2018 29;40:25. Epub 2018 Nov 29.

3National Institute of Health Sciences, Division of Genetics and Mutagenesis, Kawasaki-ku, Japan.

Background: Previously we found that DNA adducts were accumulated in the lungs of the rats exposed to ambient air in the Tokyo metropolitan area. To examine chronological change in in vivo mutagenicity of airborne particles, extracts produced from samples of total suspended particulates (TSP) collected from urban air in 1980, 1990, and 2010 in the Tokyo metropolitan area were intratracheally administered into the lungs of delta mice, and differences in mutation and mutant frequency were determined by using the assay. In vivo mutations induced by the extracts were characterized and mutation hotspots were identified by DNA sequencing of the mutated gene. Read More

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November 2018
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Prognosis Analysis of Histone Deacetylases mRNA Expression in Ovarian Cancer Patients.

J Cancer 2018 11;9(23):4547-4555. Epub 2018 Nov 11.

Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China.

Histone deacetylases modulate the dynamic balance of histone acetylation and deacetylation in cells, which participate in epigenetic regulations. Accumulated evidence has demonstrated that histone deacetylases are associated with angiogenesis, cell proliferation and survival in a variety of human cancers. However, the expression and distinct prognostic value of histone deacetylases in ovarian cancer have not been well elucidated. Read More

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November 2018
1 Read

Detection of Exon 12 and 14 Mutations in Janus Kinase 2 Gene Including a Novel Mutant in V617F Negative Polycythemia Vera Patients from Pakistan.

J Cancer 2018 21;9(23):4341-4345. Epub 2018 Oct 21.

Cancer and Medical Genetics, CAMS-A, King Saud Bin Abdulaziz University for Health Sciences & King Abdullah International Medical Research Centre (KAIMRC), King Abdulaziz Medical City, National Guard Health Affairs, Al Ahsa, Saudi Arabia.

The most frequently reported genetic aberration among polycythemia vera (PV) patients is a gain of function mutation V617F in exon 14 of Janus kinase 2 (JAK2) gene. However in many investigations, V617F negative PV patients have been reported to harbor mutations in JAK 2 exon 12. We investigated 24 patients with PV (diagnosed following 2016 WHO guidelines) to detect V617F mutation through allele specific PCR. Read More

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October 2018
2 Reads

Comprehensive Analysis of Somatic Mutation in Clear Cell Renal Cell Carcinoma to Explore Potential Mechanisms .

J Cancer 2018 18;9(22):4108-4116. Epub 2018 Oct 18.

Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.

Aim of this study was to comprehensively analyze BRCA1-associated protein-1 () somatic mutation in clear cell renal cell carcinoma (ccRCC) and explore potential therapeutic pathways and molecules. In this study, we analyzed 445 ccRCC cases from The Cancer Genome Atlas (TCGA). Comprehensive analysis including survival, transcriptome and methylation between mutated and wild-type cases was performed using bioinformatics tools . Read More

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October 2018

Efficacy of CapeOX plus Cetuximab Treatment as a First-Line Therapy for Patients with Extended RAS/BRAF/PIK3CA Wild-Type Advanced or Metastatic Colorectal Cancer.

J Cancer 2018 18;9(22):4092-4098. Epub 2018 Oct 18.

Kitakyushu General Hospital, Kitakyushu, Japan.

Oxaliplatin and capecitabine (CapeOX) combined with cetuximab is rarely used to treat advanced and metastatic colorectal cancer (mCRC). The present study aimed to clarify the clinical benefits of this treatment regimen when used as a first-line therapy in patients with expanded RAS/BRAF/PIK3CA wild-type mCRC, using the data and tumor specimens from two previously published Phase II clinical trials. The gene mutation status and clinical data of 102 patients with KRAS wild-type mCRC, who received either of CapeOX + cetuximab or FOLFOX + cetuximab, were analyzed. Read More

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October 2018

ALS-Associated E478G Mutation in Human OPTN (Optineurin) Promotes Inflammation and Induces Neuronal Cell Death.

Front Immunol 2018 14;9:2647. Epub 2018 Nov 14.

State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Shanghai, China.

Amyotrophic Lateral Sclerosis (ALS) is a group of neurodegenerative disorders that featured with the death of motor neurons, which leads to loss of voluntary control on muscles. The etiologies vary among different subtypes of ALS, and no effective management or medication could be provided to the patients, with the underlying mechanisms incompletely understood yet. Mutations in human (Optineurin), particularly E478G, have been found in many ALS patients. Read More

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November 2018

Large Interruptions of GAA Repeat Expansion Mutations in Friedreich Ataxia Are Very Rare.

Front Cell Neurosci 2018 21;12:443. Epub 2018 Nov 21.

Ataxia Research Group, Division of Biosciences, Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Uxbridge, United Kingdom.

Friedreich ataxia is a multi-system autosomal recessive inherited disorder primarily caused by homozygous GAA repeat expansion mutations within intron 1 of the frataxin gene. The resulting deficiency of frataxin protein leads to progressive mitochondrial dysfunction, oxidative stress, and cell death, with the main affected sites being the large sensory neurons of the dorsal root ganglia and the dentate nucleus of the cerebellum. The GAA repeat expansions may be pure (GAA) in sequence or may be interrupted with regions of non-GAA sequence. Read More

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November 2018

Dramatic response to alectinib in a lung cancer patient with a novel fusion and an acquired ALK T1151K mutation.

Lung Cancer (Auckl) 2018 8;9:111-116. Epub 2018 Nov 8.

Chao Family Comprehensive Cancer Center, Division of Hematology/Oncology, Department of Medicine, University of California, Irvine School of Medicine, Orange, CA, USA,

-rearranged lung cancer defines a distinctive molecular cohort of patients whose outcomes are significantly improved by the availability of ALK inhibitors. Thus, it is imperative for clinicians to screen appropriate patients for this driver mutation with a molecular testing platform capable of capturing all fusions. Here, we report a novel fusion and an ALK T1151K resistance mutation detected in a lung cancer patient who had been on crizotinib for over 8 years. Read More

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November 2018

Off- and on-target effects of genome editing in mouse embryos.

J Reprod Dev 2018 Dec 6. Epub 2018 Dec 6.

Experimental Animal Division, RIKEN BioResource Research Center, Ibaraki 305-0074, Japan.

Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas-based genome editing technology has enabled manipulation of the embryonic genome. Unbiased whole genome sequencing comparing parents to progeny has revealed that the rate of Cas9-induced mutagenesis in mouse embryos is indistinguishable from the background rate of de novo mutation. However, establishing the best practice to confirm on-target alleles of interest remains a challenge. Read More

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December 2018

Cardiac Involvement in Emery-Dreifuss Muscular Dystrophy and Related Management Strategies.

Int Heart J 2018 Dec 5. Epub 2018 Dec 5.

Department of Cardiovascular Medicine, Second Xiangya Hospital of Central South University.

Emery-Dreifuss muscular dystrophy (EDMD) is a group of hereditary muscular dystrophy syndrome caused by deficiency of genes encoding nuclear envelope proteins. Patients having EDMD show the triad of muscle dystrophy, joint contracture, and cardiac disease. In almost all patients, cardiac involvement is prevalent and is the most severe aspect of EDMD. Read More

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December 2018

A common pathomechanism in GMAP-210- and LBR-related diseases.

JCI Insight 2018 Dec 6;3(23). Epub 2018 Dec 6.

Department of Pediatrics, Medical Centre-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Biallelic loss-of-function mutations in TRIP11, encoding the golgin GMAP-210, cause the lethal human chondrodysplasia achondrogenesis 1A (ACG1A). We now find that a homozygous splice-site mutation of the lamin B receptor (LBR) gene results in the same phenotype. Intrigued by the genetic heterogeneity, we compared GMAP-210- and LBR-deficient primary cells to unravel how particular mutations in LBR cause a phenocopy of ACG1A. Read More

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December 2018

AAV CRISPR editing rescues cardiac and muscle function for 18 months in dystrophic mice.

JCI Insight 2018 Dec 6;3(23). Epub 2018 Dec 6.

Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, Missouri, USA.

Adeno-associated virus-mediated (AAV-mediated) CRISPR editing is a revolutionary approach for treating inherited diseases. Sustained, often life-long mutation correction is required for treating these diseases. Unfortunately, this has never been demonstrated with AAV CRISPR therapy. Read More

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December 2018

Cooperative effect of oncogenic MET and PIK3CA in an HGF-dominant environment in breast cancer.

Mol Cancer Ther 2018 Dec 5. Epub 2018 Dec 5.

Breast Medical Oncology, University of Texas MD Anderson Cancer Center.

There is compelling evidence that oncogenic MET and PIK3CA signaling pathways contribute to breast cancer. However, the activity of pharmacological targeting of either pathway is modest. Mechanisms of resistance to these monotherapies have not been clarified. Read More

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December 2018

Murine -linked hydrocephalus is caused by hyperpermeability of the choroid plexus.

EMBO Mol Med 2018 Dec 5. Epub 2018 Dec 5.

Cardeza Center for Vascular Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA

Though congenital hydrocephalus is heritable, it has been linked only to eight genes, one of which is Humans and mice that carry a truncated version of MPDZ incur severe hydrocephalus resulting in acute morbidity and lethality. We show by magnetic resonance imaging that contrast medium penetrates into the brain ventricles of mice carrying a loss-of-function mutation, whereas none is detected in the ventricles of normal mice, implying that the permeability of the choroid plexus epithelial cell monolayer is abnormally high. Comparative proteomic analysis of the cerebrospinal fluid of normal and hydrocephalic mice revealed up to a 53-fold increase in protein concentration, suggesting that transcytosis through the choroid plexus epithelial cells of KO mice is substantially higher than in normal mice. Read More

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December 2018
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