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Sender's message: Sepsis or genomics or altitude: JKB_daily1

Sent on Wednesday, 2014 March 26
Search: (sepsis[MeSH Terms] OR septic shock[MeSH Terms] OR altitude[MeSH Terms] OR genomics[MeSH Terms] OR genetics[MeSH Terms] OR retrotransposons[MeSH Terms] OR macrophage[MeSH Terms]) AND ("2009/8/8"[Publication Date] : "3000"[Publication Date]) AND (("Science"[Journal] OR "Nature"[Journal] OR "The New England journal of medicine"[Journal] OR "Lancet"[Journal] OR "Nature genetics"[Journal] OR "Nature medicine"[Journal]) OR (Hume DA[Author] OR Baillie JK[Author] OR Faulkner, Geoffrey J[Author]))

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Items 1 - 4 of 4

1.	Nat Genet. 2014 Feb;46(2):93. doi: 10.1038/ng.2893. Standards for clinical use of genetic variants. [No authors listed]
	PMID: 24473319 [PubMed - indexed for MEDLINE]
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2.	Nat Genet. 2014 Feb;46(2):176-81. doi: 10.1038/ng.2856. Epub 2013 Dec 22. Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma. Okosun J1, Bödör C2, Wang J3, Araf S4, Yang CY5, Pan C6, Boller S5, Cittaro D7, Bozek M8, Iqbal S4, Matthews J4, Wrench D4, Marzec J9, Tawana K4, Popov N4, O'Riain C4, O'Shea D4, Carlotti E4, Davies A10, Lawrie CH11, Matolcsy A12, Calaminici M4, Norton A13, Byers RJ14, Mein C8, Stupka E7, Lister TA4, Lenz G15, Montoto S4, Gribben JG4, Fan Y6, Grosschedl R5, Chelala C9, Fitzgibbon J4. Author information: 11] Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK. [2]. 21] Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK. [2] 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary. [3]. 31] Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK. [2]. 4Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK. 5Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany. 61] School of Biology, Georgia Institute of Technology, Atlanta, Georgia, USA. [2] Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, Georgia, USA. 7Centre for Translational Genomics and Bioinformatics, San Raffaele Scientific Institute, Milan, Italy. 8Genome Centre, Barts and the London School of Medicine and Dentistry, London, UK. 9Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK. 10Cancer Sciences Division, University of Southampton, Southampton, UK. 11Oncology Department, Biodonostia Research Institute, San Sebastian, Spain. 121st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary. 13Department of Histopathology, Christie National Health Service (NHS) Foundation Trust, Manchester, UK. 14Department of Histopathology, Manchester Royal Infirmary, Manchester, UK. 15 Department of Hematology, Oncology and Tumor Immunology, Charité Universitätsmedizin, Berlin, Germany. Abstract Follicular lymphoma is an incurable malignancy, with transformation to an aggressive subtype representing a critical event during disease progression. Here we performed whole-genome or whole-exome sequencing on 10 follicular lymphoma-transformed follicular lymphoma pairs followed by deep sequencing of 28 genes in an extension cohort, and we report the key events and evolutionary processes governing tumor initiation and transformation. Tumor evolution occurred through either a 'rich' or 'sparse' ancestral common progenitor clone (CPC). We identified recurrent mutations in linker histone, JAK-STAT signaling, NF-κB signaling and B cell developmental genes. Longitudinal analyses identified early driver mutations in chromatin regulator genes (CREBBP, EZH2 and KMT2D (MLL2)), whereas mutations in EBF1 and regulators of NF-κB signaling (MYD88 and TNFAIP3) were gained at transformation. Collectively, this study provides new insights into the genetic basis of follicular lymphoma and the clonal dynamics of transformation and suggests that personalizing therapies to target key genetic alterations in the CPC represents an attractive therapeutic strategy. PMCID: PMC3907271 [Available on 2014/8/1]
	PMID: 24362818 [PubMed - indexed for MEDLINE]
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3.	Nat Genet. 2014 Feb;46(2):200-4. doi: 10.1038/ng.2852. Epub 2013 Dec 15. Meta-analysis of gene-level tests for rare variant association. Liu DJ1, Peloso GM2, Zhan X1, Holmen OL3, Zawistowski M4, Feng S4, Nikpay M5, Auer PL6, Goel A7, Zhang H8, Peters U9, Farrall M7, Orho-Melander M10, Kooperberg C11, McPherson R5, Watkins H7, Willer CJ8, Hveem K12, Melander O10, Kathiresan S13, Abecasis GR1. Author information: 11] Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA. [2]. 21] Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. [2] Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA. [3] Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA. [4]. 31] HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway. [2] St. Olav Hospital, Trondheim University Hospital, Trondheim, Norway. [3]. 4Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA. 5University of Ottawa Heart Institute, Ottawa, Ontario, Canada. 61] Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. [2] School of Public Health, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin, USA. 71] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. [2] Department of Cardiovascular Medicine, University of Oxford, Oxford, UK. 81] Division of Cardiology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA. [2] Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, USA. 91] Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. [2] Department of Epidemiology, University of Washington School of Public Health, Seattle, Washington, USA. 101] Department of Cardiovascular Medicine, University of Oxford, Oxford, UK. [2] Department of Clinical Sciences, Lund University, Malmö, Sweden. 111] Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. [2] Department of Biostatistics, University of Washington School of Public Health, Seattle, Washington, USA. 121] HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway. [2] Department of Medicine, Levanger Hospital, Nord-Trøndelag Health Trust, Levanger, Norway. 131] Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. [2] Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA. [3] Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA. [4] Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA. [5]. Abstract The majority of reported complex disease associations for common genetic variants have been identified through meta-analysis, a powerful approach that enables the use of large sample sizes while protecting against common artifacts due to population structure and repeated small-sample analyses sharing individual-level data. As the focus of genetic association studies shifts to rare variants, genes and other functional units are becoming the focus of analysis. Here we propose and evaluate new approaches for performing meta-analysis of rare variant association tests, including burden tests, weighted burden tests, variable-threshold tests and tests that allow variants with opposite effects to be grouped together. We show that our approach retains useful features from single-variant meta-analysis approaches and demonstrate its use in a study of blood lipid levels in ∼18,500 individuals genotyped with exome arrays. PMCID: PMC3939031 [Available on 2014/8/1]
	PMID: 24336170 [PubMed - indexed for MEDLINE]
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4.	Nat Genet. 2014 Feb;46(2):152-60. doi: 10.1038/ng.2853. Epub 2013 Dec 15. Therapeutic modulation of eIF2α phosphorylation rescues TDP-43 toxicity in amyotrophic lateral sclerosis disease models. Kim HJ1, Raphael AR2, LaDow ES3, McGurk L4, Weber RA4, Trojanowski JQ5, Lee VM5, Finkbeiner S3, Gitler AD2, Bonini NM4. Author information: 11] Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. [2]. 2Department of Genetics, Stanford University School of Medicine, Stanford, California, USA. 3Gladstone Institute of Neurological Disease, San Francisco, California, USA. 4Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 5Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Abstract Amyotrophic lateral sclerosis (ALS) is a fatal, late-onset neurodegenerative disease primarily affecting motor neurons. A unifying feature of many proteins associated with ALS, including TDP-43 and ataxin-2, is that they localize to stress granules. Unexpectedly, we found that genes that modulate stress granules are strong modifiers of TDP-43 toxicity in Saccharomyces cerevisiae and Drosophila melanogaster. eIF2α phosphorylation is upregulated by TDP-43 toxicity in flies, and TDP-43 interacts with a central stress granule component, polyA-binding protein (PABP). In human ALS spinal cord neurons, PABP accumulates abnormally, suggesting that prolonged stress granule dysfunction may contribute to pathogenesis. We investigated the efficacy of a small molecule inhibitor of eIF2α phosphorylation in ALS models. Treatment with this inhibitor mitigated TDP-43 toxicity in flies and mammalian neurons. These findings indicate that the dysfunction induced by prolonged stress granule formation might contribute directly to ALS and that compounds that mitigate this process may represent a novel therapeutic approach. PMCID: PMC3934366 [Available on 2014/8/1]
	PMID: 24336168 [PubMed - indexed for MEDLINE]
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What's new for 'JKB_daily1' in PubMed

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Sender's message: Sepsis or genomics or altitude: JKB_daily1

Sent on Saturday, 2014 March 22
Search: (sepsis[MeSH Terms] OR septic shock[MeSH Terms] OR altitude[MeSH Terms] OR genomics[MeSH Terms] OR genetics[MeSH Terms] OR retrotransposons[MeSH Terms] OR macrophage[MeSH Terms]) AND ("2009/8/8"[Publication Date] : "3000"[Publication Date]) AND (("Science"[Journal] OR "Nature"[Journal] OR "The New England journal of medicine"[Journal] OR "Lancet"[Journal] OR "Nature genetics"[Journal] OR "Nature medicine"[Journal]) OR (Hume DA[Author] OR Baillie JK[Author] OR Faulkner, Geoffrey J[Author]))

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PubMed Results

Items 1 - 5 of 5

1.	N Engl J Med. 2014 Mar 13;370(11):988-90. doi: 10.1056/NEJMp1310471. Incidentalomas in genomics and radiology. Solomon BD. Author information: From the Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD, and the Inova Translational Medicine Institute, Falls Church, VA.
	PMID: 24620864 [PubMed - indexed for MEDLINE]
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2.	Science. 2014 Mar 7;343(6175):1154-8. doi: 10.1126/science.1244325. Altitudinal changes in malaria incidence in highlands of Ethiopia and Colombia. Siraj AS1, Santos-Vega M, Bouma MJ, Yadeta D, Ruiz Carrascal D, Pascual M. Author information: 1Department of Geography and the Environment, University of Denver, 235 Boettcher West, 2050 East Iliff Avenue Denver, CO 80208-0710, USA. Abstract The impact of global warming on insect-borne diseases and on highland malaria in particular remains controversial. Temperature is known to influence transmission intensity through its effects on the population growth of the mosquito vector and on pathogen development within the vector. Spatiotemporal data at a regional scale in highlands of Colombia and Ethiopia supplied an opportunity to examine how the spatial distribution of the disease changes with the interannual variability of temperature. We provide evidence for an increase in the altitude of malaria distribution in warmer years, which implies that climate change will, without mitigation, result in an increase of the malaria burden in the densely populated highlands of Africa and South America.
	PMID: 24604201 [PubMed - indexed for MEDLINE]
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3.	Science. 2014 Mar 7;343(6175):1072-3, 1075. doi: 10.1126/science.343.6175.1072. Structural biology scales down. Service RF.
	PMID: 24604178 [PubMed - indexed for MEDLINE]
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4.	Nature. 2014 Mar 6;507(7490):57-61. doi: 10.1038/nature13087. Epub 2014 Feb 26. A predictive fitness model for influenza. Luksza M1, Lässig M2. Author information: 11] Institute for Theoretical Physics, University of Cologne, Zülpicher Strasse 77, 50937 Köln, Germany [2] Biological Sciences, Columbia University, 607D Fairchild Center, New York, New York 10027, USA. 2Institute for Theoretical Physics, University of Cologne, Zülpicher Strasse 77, 50937 Köln, Germany. Comment in Influenza: Prediction is worth a shot. [Nature. 2014] Influenza: Prediction is worth a shot.Koelle K, Rasmussen DA. Nature. 2014 Mar 6; 507(7490):47-8. Epub 2014 Feb 26. Abstract The seasonal human influenza A/H3N2 virus undergoes rapid evolution, which produces significant year-to-year sequence turnover in the population of circulating strains. Adaptive mutations respond to human immune challenge and occur primarily in antigenic epitopes, the antibody-binding domains of the viral surface protein haemagglutinin. Here we develop a fitness model for haemagglutinin that predicts the evolution of the viral population from one year to the next. Two factors are shown to determine the fitness of a strain: adaptive epitope changes and deleterious mutations outside the epitopes. We infer both fitness components for the strains circulating in a given year, using population-genetic data of all previous strains. From fitness and frequency of each strain, we predict the frequency of its descendent strains in the following year. This fitness model maps the adaptive history of influenza A and suggests a principled method for vaccine selection. Our results call for a more comprehensive epidemiology of influenza and other fast-evolving pathogens that integrates antigenic phenotypes with other viral functions coupled by genetic linkage.
	PMID: 24572367 [PubMed - indexed for MEDLINE]
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5.	Nature. 2014 Mar 6;507(7490):104-8. doi: 10.1038/nature12942. Epub 2014 Jan 26. Citrullination regulates pluripotency and histone H1 binding to chromatin. Christophorou MA1, Castelo-Branco G2, Halley-Stott RP3, Oliveira CS4, Loos R5, Radzisheuskaya A6, Mowen KA7, Bertone P8, Silva JC6, Zernicka-Goetz M9, Nielsen ML10, Gurdon JB3, Kouzarides T11. Author information: 11] The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK [2]. 21] The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK [2] Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden [3]. 31] The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK [2] Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK. 41] The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK [2] EMBRAPA Dairy Cattle Research Center, Juiz de Fora, Brazil [3] Department of Physiology, Development and Neuroscience, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK. 5European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SD, UK. 61] Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK [2] Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK. 7Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California 92037, USA. 81] European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SD, UK [2] Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK [3] Genome Biology and Developmental Biology Units, European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany. 91] The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK [2] Department of Physiology, Development and Neuroscience, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK. 10Department of proteomics, The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Faculty of Health Sciences, Blegdamsvej 3b, DK-2200 Copenhagen, Denmark. 111] The Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK [2] Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK. Abstract Citrullination is the post-translational conversion of an arginine residue within a protein to the non-coded amino acid citrulline. This modification leads to the loss of a positive charge and reduction in hydrogen-bonding ability. It is carried out by a small family of tissue-specific vertebrate enzymes called peptidylarginine deiminases (PADIs) and is associated with the development of diverse pathological states such as autoimmunity, cancer, neurodegenerative disorders, prion diseases and thrombosis. Nevertheless, the physiological functions of citrullination remain ill-defined, although citrullination of core histones has been linked to transcriptional regulation and the DNA damage response. PADI4 (also called PAD4 or PADV), the only PADI with a nuclear localization signal, was previously shown to act in myeloid cells where it mediates profound chromatin decondensation during the innate immune response to infection. Here we show that the expression and enzymatic activity of Padi4 are also induced under conditions of ground-state pluripotency and during reprogramming in mouse. Padi4 is part of the pluripotency transcriptional network, binding to regulatory elements of key stem-cell genes and activating their expression. Its inhibition lowers the percentage of pluripotent cells in the early mouse embryo and significantly reduces reprogramming efficiency. Using an unbiased proteomic approach we identify linker histone H1 variants, which are involved in the generation of compact chromatin, as novel PADI4 substrates. Citrullination of a single arginine residue within the DNA-binding site of H1 results in its displacement from chromatin and global chromatin decondensation. Together, these results uncover a role for citrullination in the regulation of pluripotency and provide new mechanistic insights into how citrullination regulates chromatin compaction.
	PMID: 24463520 [PubMed - indexed for MEDLINE]
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What's new for 'JKB_daily1' in PubMed

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Sender's message: Sepsis or genomics or altitude: JKB_daily1

Sent on Wednesday, 2014 March 19
Search: (sepsis[MeSH Terms] OR septic shock[MeSH Terms] OR altitude[MeSH Terms] OR genomics[MeSH Terms] OR genetics[MeSH Terms] OR retrotransposons[MeSH Terms] OR macrophage[MeSH Terms]) AND ("2009/8/8"[Publication Date] : "3000"[Publication Date]) AND (("Science"[Journal] OR "Nature"[Journal] OR "The New England journal of medicine"[Journal] OR "Lancet"[Journal] OR "Nature genetics"[Journal] OR "Nature medicine"[Journal]) OR (Hume DA[Author] OR Baillie JK[Author] OR Faulkner, Geoffrey J[Author]))

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1.	Nat Med. 2014 Jan;20(1):2. doi: 10.1038/nm0114-2. Revved-up epigenetic sequencing may foster new diagnostics. Duhaime-Ross A.
	PMID: 24398946 [PubMed - indexed for MEDLINE]
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2.	Nat Med. 2014 Jan;20(1):1. doi: 10.1038/nm.3456. Finding common ground in cancer research. [No authors listed]
	PMID: 24398945 [PubMed - indexed for MEDLINE]
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What's new for 'JKB_daily1' in PubMed

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Sender's message: Sepsis or genomics or altitude: JKB_daily1

Sent on Friday, 2014 March 14
Search: (sepsis[MeSH Terms] OR septic shock[MeSH Terms] OR altitude[MeSH Terms] OR genomics[MeSH Terms] OR genetics[MeSH Terms] OR retrotransposons[MeSH Terms] OR macrophage[MeSH Terms]) AND ("2009/8/8"[Publication Date] : "3000"[Publication Date]) AND (("Science"[Journal] OR "Nature"[Journal] OR "The New England journal of medicine"[Journal] OR "Lancet"[Journal] OR "Nature genetics"[Journal] OR "Nature medicine"[Journal]) OR (Hume DA[Author] OR Baillie JK[Author] OR Faulkner, Geoffrey J[Author]))

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Items 1 - 7 of 7

1.	Lancet. 2014 Mar 1;383(9919):775. doi: 10.1016/S0140-6736(14)60393-7. James Watson: thinking outside the genome. Watts G.
	PMID: 24581658 [PubMed - indexed for MEDLINE]
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2.	Nature. 2014 Feb 27;506(7489):445-50. doi: 10.1038/nature13108. Epub 2014 Feb 19. Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. Mack SC1, Witt H2, Piro RM3, Gu L4, Zuyderduyn S5, Stütz AM6, Wang X7, Gallo M8, Garzia L8, Zayne K8, Zhang X9, Ramaswamy V7, Jäger N4, Jones DT10, Sill M11, Pugh TJ12, Ryzhova M10, Wani KM13, Shih DJ7, Head R8, Remke M7, Bailey SD14, Zichner T6, Faria CC8, Barszczyk M7, Stark S10, Seker-Cin H10, Hutter S10, Johann P10, Bender S10, Hovestadt V3, Tzaridis T10, Dubuc AM7, Northcott PA10, Peacock J7, Bertrand KC7, Agnihotri S8, Cavalli FM8, Clarke I8, Nethery-Brokx K8, Creasy CL15, Verma SK15, Koster J16, Wu X8, Yao Y7, Milde T17, Sin-Chan P8, Zuccaro J8, Lau L8, Pereira S8, Castelo-Branco P8, Hirst M18, Marra MA19, Roberts SS20, Fults D21, Massimi L22, Cho YJ23, Van Meter T24, Grajkowska W25, Lach B26, Kulozik AE27, von Deimling A28, Witt O17, Scherer SW8, Fan X29, Muraszko KM30, Kool M10, Pomeroy SL12, Gupta N31, Phillips J32, Huang A33, Tabori U33, Hawkins C7, Malkin D34, Kongkham PN35, Weiss WA32, Jabado N36, Rutka JT35, Bouffet E37, Korbel JO38, Lupien M39, Aldape KD13, Bader GD5, Eils R4, Lichter P3, Dirks PB40, Pfister SM41, Korshunov A42, Taylor MD35. Author information: 11] Developmental & Stem Cell Biology Program, Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada [2] Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada [3] Division of Neurosurgery, University of Toronto, Toronto, Ontario M5S 1A8, Canada [4]. 21] Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany [2] Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg 69120, Germany [3] German Cancer Consortium (DKTK), Heidelberg 69120, Germany [4]. 31] German Cancer Consortium (DKTK), Heidelberg 69120, Germany [2] Division of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. 41] German Cancer Consortium (DKTK), Heidelberg 69120, Germany [2] Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. 5Department of Molecular Genetics, Banting and Best Department of Medical Research, The Donnelly Centre, University of Toronto, Toronto, Ontario M4N 1X8, Canada. 61] German Cancer Consortium (DKTK), Heidelberg 69120, Germany [2] Genome Biology, European Molecular Biology, Laboratory Meyerhofstr. 1, Heidelberg 69117, Germany. 71] Developmental & Stem Cell Biology Program, Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada [2] Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada. 8Developmental & Stem Cell Biology Program, Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada. 9Department of Genetics, Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA. 101] Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany [2] German Cancer Consortium (DKTK), Heidelberg 69120, Germany. 111] German Cancer Consortium (DKTK), Heidelberg 69120, Germany [2] Division of Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. 12Department of Neurology, Harvard Medical School, Children's Hospital Boston, MIT, Boston, Massachusetts 02115, USA. 13Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. 141] Ontario Cancer Institute, Princess Margaret Cancer Centre-University Health Network, Toronto, Ontario M5G 1L7, Canada [2] Ontario Institute for Cancer Research, Toronto, Ontario M5G 1L7, Canada. 15Cancer Epigenetics Discovery Performance Unit, GlaxoSmithKline Pharmaceuticals, Collegeville, Pennsylvania 19426, USA. 16Department of Oncogenomics, Academic Medical Center, Amsterdam 1105, The Netherlands. 171] Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg 69120, Germany [2] German Cancer Consortium (DKTK), Heidelberg 69120, Germany [3] CCU Pediatric Oncology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. 181] Centre for High-Throughput Biology, Department of Microbiology & Immunology, University of British Columbia, Vancouver, V6T 1Z4 British Columbia, Canada [2] Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada. 191] Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada [2] Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6H 3N1, Canada. 20Department of Pediatrics and National Capital Consortium, Uniformed Services University, Bethesda, Maryland 20814, USA. 21Department of Neurosurgery, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA. 22Pediatric Neurosurgery, Catholic University Medical School, Gemelli Hospital, Rome 00168, Italy. 23Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA. 24Department of Pediatrics, Virginia Commonwealth, Richmond, Virginia 23298-0646, USA. 25Department of Pathology, University of Warsaw, Children's Memorial Health Institute University of Warsaw, Warsaw 04-730, Poland. 26Division of Anatomical Pathology, Department of Pathology and Molecular Medicine, McMaster University, Hamilton General Hospital, Hamilton, Ontario L8S 4K1, Canada. 271] Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg 69120, Germany [2] German Cancer Consortium (DKTK), Heidelberg 69120, Germany. 281] German Cancer Consortium (DKTK), Heidelberg 69120, Germany [2] Department of Neuropathology Ruprecht-Karls-University Heidelberg, Institute of Pathology, Heidelberg 69120, Germany. 291] University of Michigan Cell and Developmental Biology, Ann Arbor, Michigan 48109-2200, USA [2] Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. 30Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. 31Department of Neurosurgery, University of California San Francisco, San Francisco, California 94143-0112, USA. 32Departments of Neurology, Pediatrics, and Neurosurgery, University of California, San Francisco, The Helen Diller Family Cancer Research Building, San Francisco, California 94158, USA. 331] Developmental & Stem Cell Biology Program, Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada [2] Department of Neuro-oncology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada. 34Department of Haematology and Oncology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada. 351] Developmental & Stem Cell Biology Program, Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada [2] Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada [3] Division of Neurosurgery, University of Toronto, Toronto, Ontario M5S 1A8, Canada. 36Departments of Pediatrics and Human Genetics, McGill University and the McGill University Health Center Research Institute, Montreal, Quebec H3Z 2Z3, Canada. 37Department of Neuro-oncology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada. 38Genome Biology, European Molecular Biology, Laboratory Meyerhofstr. 1, Heidelberg 69117, Germany. 391] Ontario Cancer Institute, Princess Margaret Cancer Centre-University Health Network, Toronto, Ontario M5G 1L7, Canada [2] Ontario Institute for Cancer Research, Toronto, Ontario M5G 1L7, Canada [3] Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1X8, Canada. 401] Developmental & Stem Cell Biology Program, Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario M5G 1L7, Canada [2] Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada [3] Division of Neurosurgery, University of Toronto, Toronto, Ontario M5S 1A8, Canada [4] Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. 411] Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany [2] Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg 69120, Germany [3] German Cancer Consortium (DKTK), Heidelberg 69120, Germany. 421] German Cancer Consortium (DKTK), Heidelberg 69120, Germany [2] University of Michigan Cell and Developmental Biology, Ann Arbor, Michigan 48109-2200, USA [3] CCU Neuropathology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. Comment in Cancer: Tumours outside the mutation box. [Nature. 2014] Cancer: Tumours outside the mutation box.Versteeg R. Nature. 2014 Feb 27; 506(7489):438-9. Epub 2014 Feb 19. Abstract Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.
	PMID: 24553142 [PubMed - indexed for MEDLINE]
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3.	Nature. 2014 Feb 27;506(7489):456-62. doi: 10.1038/nature13044. Epub 2014 Feb 19. A Crohn's disease variant in Atg16l1 enhances its degradation by caspase 3. Murthy A1, Li Y1, Peng I1, Reichelt M2, Katakam AK2, Noubade R1, Roose-Girma M3, DeVoss J1, Diehl L2, Graham RR4, van Lookeren Campagne M1. Author information: 1Department of Immunology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA. 2Department of Pathology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA. 3Department of Molecular Biology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA. 4ITGR Human Genetics, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA. Comment in Cell biology: Stressful genetics in Crohn's disease. [Nature. 2014] Cell biology: Stressful genetics in Crohn's disease.Kaser A, Blumberg RS. Nature. 2014 Feb 27; 506(7489):441-2. Epub 2014 Feb 19. Abstract Crohn's disease is a debilitating inflammatory bowel disease (IBD) that can involve the entire digestive tract. A single-nucleotide polymorphism (SNP) encoding a missense variant in the autophagy gene ATG16L1 (rs2241880, Thr300Ala) is strongly associated with the incidence of Crohn's disease. Numerous studies have demonstrated the effect of ATG16L1 deletion or deficiency; however, the molecular consequences of the Thr300Ala (T300A) variant remains unknown. Here we show that amino acids 296-299 constitute a caspase cleavage motif in ATG16L1 and that the T300A variant (T316A in mice) significantly increases ATG16L1 sensitization to caspase-3-mediated processing. We observed that death-receptor activation or starvation-induced metabolic stress in human and murine macrophages increased degradation of the T300A or T316A variants of ATG16L1, respectively, resulting in diminished autophagy. Knock-in mice harbouring the T316A variant showed defective clearance of the ileal pathogen Yersinia enterocolitica and an elevated inflammatory cytokine response. In turn, deletion of the caspase-3-encoding gene, Casp3, or elimination of the caspase cleavage site by site-directed mutagenesis rescued starvation-induced autophagy and pathogen clearance, respectively. These findings demonstrate that caspase 3 activation in the presence of a common risk allele leads to accelerated degradation of ATG16L1, placing cellular stress, apoptotic stimuli and impaired autophagy in a unified pathway that predisposes to Crohn's disease.
	PMID: 24553140 [PubMed - indexed for MEDLINE]
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4.	Nature. 2014 Feb 27;506(7489):503-6. doi: 10.1038/nature12902. Epub 2014 Jan 19. Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity. Westphalen K1, Gusarova GA1, Islam MN1, Subramanian M2, Cohen TS3, Prince AS3, Bhattacharya J4. Author information: 1Lung Biology Laboratory, Department of Medicine, Division of Pulmonary, Allergy and Critical Care, Columbia University Medical Center, New York, New York 10032, USA. 2Department of Medicine, Division of Molecular Medicine, Columbia University Medical Center, New York, New York 10032, USA. 3Department of Pediatrics, Columbia University Medical Center, New York, New York 10032, USA. 41] Lung Biology Laboratory, Department of Medicine, Division of Pulmonary, Allergy and Critical Care, Columbia University Medical Center, New York, New York 10032, USA [2] Department of Physiology & Cellular Biophysics, College of Physicians and Surgeons, Columbia University Medical Center, New York, New York 10032, USA. Abstract The tissue-resident macrophages of barrier organs constitute the first line of defence against pathogens at the systemic interface with the ambient environment. In the lung, resident alveolar macrophages (AMs) provide a sentinel function against inhaled pathogens. Bacterial constituents ligate Toll-like receptors (TLRs) on AMs, causing AMs to secrete proinflammatory cytokines that activate alveolar epithelial receptors, leading to recruitment of neutrophils that engulf pathogens. Because the AM-induced response could itself cause tissue injury, it is unclear how AMs modulate the response to prevent injury. Here, using real-time alveolar imaging in situ, we show that a subset of AMs attached to the alveolar wall form connexin 43 (Cx43)-containing gap junction channels with the epithelium. During lipopolysaccharide-induced inflammation, the AMs remained sessile and attached to the alveoli, and they established intercommunication through synchronized Ca(2+) waves, using the epithelium as the conducting pathway. The intercommunication was immunosuppressive, involving Ca(2+)-dependent activation of Akt, because AM-specific knockout of Cx43 enhanced alveolar neutrophil recruitment and secretion of proinflammatory cytokines in the bronchoalveolar lavage. A picture emerges of a novel immunomodulatory process in which a subset of alveolus-attached AMs intercommunicates immunosuppressive signals to reduce endotoxin-induced lung inflammation.
	PMID: 24463523 [PubMed - indexed for MEDLINE]
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5.	Nature. 2014 Feb 27;506(7489):494-7. doi: 10.1038/nature12904. Epub 2014 Jan 8. Genetics of single-cell protein abundance variation in large yeast populations. Albert FW1, Treusch S2, Shockley AH3, Bloom JS4, Kruglyak L5. Author information: 11] Department of Human Genetics, University of California, Los Angeles, California 90095, USA [2] Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA. 2Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA. 3Synthetic Genomics, 11149 North Torrey Pines Road, La Jolla, California 92037, USA. 41] Department of Human Genetics, University of California, Los Angeles, California 90095, USA [2] Howard Hughes Medical Institute, University of California, Los Angeles, California 90095, USA. 51] Department of Human Genetics, University of California, Los Angeles, California 90095, USA [2] Howard Hughes Medical Institute, University of California, Los Angeles, California 90095, USA [3] Department of Biological Chemistry, University of California, Los Angeles, California 90095, USA. Abstract Variation among individuals arises in part from differences in DNA sequences, but the genetic basis for variation in most traits, including common diseases, remains only partly understood. Many DNA variants influence phenotypes by altering the expression level of one or several genes. The effects of such variants can be detected as expression quantitative trait loci (eQTL). Traditional eQTL mapping requires large-scale genotype and gene expression data for each individual in the study sample, which limits sample sizes to hundreds of individuals in both humans and model organisms and reduces statistical power. Consequently, many eQTL are probably missed, especially those with smaller effects. Furthermore, most studies use messenger RNA rather than protein abundance as the measure of gene expression. Studies that have used mass-spectrometry proteomics reported unexpected differences between eQTL and protein QTL (pQTL) for the same genes, but these studies have been even more limited in scope. Here we introduce a powerful method for identifying genetic loci that influence protein expression in the yeast Saccharomyces cerevisiae. We measure single-cell protein abundance through the use of green fluorescent protein tags in very large populations of genetically variable cells, and use pooled sequencing to compare allele frequencies across the genome in thousands of individuals with high versus low protein abundance. We applied this method to 160 genes and detected many more loci per gene than previous studies. We also observed closer correspondence between loci that influence protein abundance and loci that influence mRNA abundance of a given gene. Most loci that we detected were clustered in 'hotspots' that influence multiple proteins, and some hotspots were found to influence more than half of the proteins that we examined. The variants that underlie these hotspots have profound effects on the gene regulatory network and provide insights into genetic variation in cell physiology between yeast strains.
	PMID: 24402228 [PubMed - indexed for MEDLINE]
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6.	Nature. 2014 Feb 20;506(7488):371-5. doi: 10.1038/nature12881. Epub 2013 Dec 25. Landscape of genomic alterations in cervical carcinomas. Ojesina AI1, Lichtenstein L2, Freeman SS3, Pedamallu CS4, Imaz-Rosshandler I5, Pugh TJ4, Cherniack AD3, Ambrogio L3, Cibulskis K3, Bertelsen B6, Romero-Cordoba S5, Treviño V7, Vazquez-Santillan K5, Guadarrama AS5, Wright AA8, Rosenberg MW 3, Duke F9, Kaplan B4, Wang R10, Nickerson E3, Walline HM11, Lawrence MS3, Stewart C3, Carter SL3, McKenna A3, Rodriguez-Sanchez IP12, Espinosa-Castilla M5, Woie K13, Bjorge L14, Wik E14, Halle MK14, Hoivik EA14, Krakstad C14, Gabiño NB5, Gómez-Macías GS12, Valdez-Chapa LD12, Garza-Rodríguez ML12, Maytorena G15, Vazquez J15, Rodea C15, Cravioto A15, Cortes ML3, Greulich H16, Crum CP17, Neuberg DS18, Hidalgo-Miranda A 5, Escareno CR19, Akslen LA20, Carey TE21, Vintermyr OK20, Gabriel SB3, Barrera-Saldaña HA 12, Melendez-Zajgla J5, Getz G22, Salvesen HB23, Meyerson M24. Author information: 11] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA [3]. 21] The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA [2]. 3The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA. 41] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA. 5Instituto Nacional de Medicina Genomica, Mexico City 14610, Mexico. 6Department of Pathology, Haukeland University Hospital, N5021 Bergen, Norway. 7Tecnológico de Monterrey, Monterrey 64849, Mexico. 81] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. 9Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA. 101] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China. 11Cancer Biology Program, Program in the Biomedical Sciences, Rackham Graduate School, University of Michigan, Ann Arbor, Michigan 48109, USA. 12Facultad de Medicina y Hospital Universitario 'Dr. José Eluterio González' de la Universidad Autónoma de Nuevo León, Monterrey, Nuevo León 64460, México. 13Department of Obstetrics and Gynecology, Haukeland University Hospital, N5021 Bergen, Norway. 141] Department of Obstetrics and Gynecology, Haukeland University Hospital, N5021 Bergen, Norway [2] Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, N5020 Bergen, Norway. 15Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico. 161] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA [3] Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. 17Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. 18Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA. 191] Instituto Nacional de Medicina Genomica, Mexico City 14610, Mexico [2] Claremont Graduate University, Claremont, California 91711, USA. 201] Department of Pathology, Haukeland University Hospital, N5021 Bergen, Norway [2] Centre for Cancer Biomarkers, Department of Clinical Medicine, University of Bergen, N5020 Bergen, Norway. 21Head and Neck Oncology Program and Department of Otolaryngology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 38109, USA. 221] The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA [2] Massachusetts General Hospital Cancer Center and Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. 231] Department of Obstetrics and Gynecology, Haukeland University Hospital, N5021 Bergen, Norway [2] Department of Clinical Science, Centre for Cancer Biomarkers, University of Bergen, N5020 Bergen, Norway [3]. 241] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts 02142, USA [3] Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA [4]. Abstract Cervical cancer is responsible for 10-15% of cancer-related deaths in women worldwide. The aetiological role of infection with high-risk human papilloma viruses (HPVs) in cervical carcinomas is well established. Previous studies have also implicated somatic mutations in PIK3CA, PTEN, TP53, STK11 and KRAS as well as several copy-number alterations in the pathogenesis of cervical carcinomas. Here we report whole-exome sequencing analysis of 115 cervical carcinoma-normal paired samples, transcriptome sequencing of 79 cases and whole-genome sequencing of 14 tumour-normal pairs. Previously unknown somatic mutations in 79 primary squamous cell carcinomas include recurrent E322K substitutions in the MAPK1 gene (8%), inactivating mutations in the HLA-B gene (9%), and mutations in EP300 (16%), FBXW7 (15%), NFE2L2 (4%), TP53 (5%) and ERBB2 (6%). We also observe somatic ELF3 (13%) and CBFB (8%) mutations in 24 adenocarcinomas. Squamous cell carcinomas have higher frequencies of somatic nucleotide substitutions occurring at cytosines preceded by thymines (Tp*C sites) than adenocarcinomas. Gene expression levels at HPV integration sites were statistically significantly higher in tumours with HPV integration compared with expression of the same genes in tumours without viral integration at the same site. These data demonstrate several recurrent genomic alterations in cervical carcinomas that suggest new strategies to combat this disease.
	PMID: 24390348 [PubMed - indexed for MEDLINE]
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7.	Lancet. 2014 Mar 1;383(9919):828-40. doi: 10.1016/S0140-6736(13)60630-3. Epub 2013 Aug 6. Genetics of dementia. Loy CT1, Schofield PR2, Turner AM3, Kwok JB4. Author information: 1School of Public Health, University of Sydney, Sydney, NSW, Australia; Neuroscience Research Australia, Randwick, NSW, Australia; Huntington Disease Service, Westmead Hospital, Westmead, NSW, Australia. 2Neuroscience Research Australia, Randwick, NSW, Australia; University of New South Wales, Kensington, NSW, Australia. 3Department of Medical Genetics, Sydney Children's Hospital, Randwick, NSW, Australia. 4Neuroscience Research Australia, Randwick, NSW, Australia; University of New South Wales, Kensington, NSW, Australia. Electronic address: j.kwok@neura.edu.au. Abstract 25% of all people aged 55 years and older have a family history of dementia. For most, the family history is due to genetically complex disease, where many genetic variations of small effect interact to increase risk of dementia. The lifetime risk of dementia for these families is about 20%, compared with 10% in the general population. A small proportion of families have an autosomal dominant family history of early-onset dementia, which is often due to mendelian disease, caused by a mutation in one of the dementia genes. Each family member has a 50% chance of inheriting the mutation, which confers a lifetime dementia risk of over 95%. In this Review, we focus on the evidence for, and the approach to, genetic testing in Alzheimer's disease (APP, PSEN1, and PSEN2 genes), frontotemporal dementia (MAPT, GRN, C9ORF72, and other genes), and other familial dementias. We conclude by discussing the practical aspects of genetic counselling. Copyright © 2014 Elsevier Ltd. All rights reserved.
	PMID: 23927914 [PubMed - indexed for MEDLINE]
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