40,718 results match your criteria Cancer Genomics & Proteomics[Journal]


Interplay between miRNAs and host genes and their role in cancer.

Brief Funct Genomics 2019 Feb 20. Epub 2019 Feb 20.

Center for Quantitative Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.

MicroRNAs (miRNAs) are small endogenous non-coding functional RNAs that post-transcriptionally regulate gene expression. They play essential roles in nearly all biological processes including cell development and differentiation, DNA damage repair, cell death as well as intercellular communication. They are highly involved in cancer, acting as tumor suppressors and/or promoters to modulate cell proliferation, epithelial-mesenchymal transition and tumor invasion and metastasis. Read More

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https://academic.oup.com/bfg/advance-article/doi/10.1093/bfg
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http://dx.doi.org/10.1093/bfgp/elz002DOI Listing
February 2019
1 Read

Involuntary smoking and the risk of head and neck cancer in an East Asian population.

Cancer Epidemiol 2019 Feb 19;59:173-177. Epub 2019 Feb 19.

Division of Public Health, Department of Family and Preventive Medicine, University of Utah School of Medicine, and Huntsman Cancer Institute, Salt Lake City, UT, United States.

Background: Although tobacco involuntary smoking is an established risk factor for lung cancer, the association with head and neck cancer (HNC) is not established. We aimed to investigate this potential association in an East Asian population.

Methods: We conducted a multicenter case-control study in East Asia including eight centers. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S18777821183056
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http://dx.doi.org/10.1016/j.canep.2019.01.020DOI Listing
February 2019
1 Read

Negotiating jurisdictional boundaries in response to new genetic possibilities in breast cancer care: The creation of an 'oncogenetic taskscape'.

Soc Sci Med 2019 Feb 13;225:26-33. Epub 2019 Feb 13.

Ethox Centre and Wellcome Centre for Ethics and Humanities, Nuffield Department of Population Health, Big Data Institute University of Oxford, UK.

Changes in the nature and structure of healthcare pathways have implications for healthcare professionals' jurisdictional boundaries. The introduction of treatment focused BRCA1 and 2 genetic testing (TFGT) for newly diagnosed patients with breast cancer offers a contemporary example of pathway change brought about by technological advancements in gene testing and clinical evidence, and reflects the cultural shift towards genomics. Forming part of an ethnographically informed study of patient and practitioner experiences of TFGT at a UK teaching hospital, this paper focuses on the impact of a proposal to pilot a mainstreamed TFGT pathway on healthcare professionals' negotiations of professional jurisdiction. Read More

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http://dx.doi.org/10.1016/j.socscimed.2019.02.020DOI Listing
February 2019

Uncovering genetic mechanisms of kidney aging through transcriptomics, genomics, and epigenomics.

Kidney Int 2019 Mar;95(3):624-635

Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Medicine, Biology and Health, University of Manchester, Manchester, UK; Division of Medicine and Manchester Heart Centre, Manchester University National Health Service Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK. Electronic address:

Nephrons scar and involute during aging, increasing the risk of chronic kidney disease. Little is known, however, about genetic mechanisms of kidney aging. We sought to define the signatures of age on the renal transcriptome using 563 human kidneys. Read More

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http://dx.doi.org/10.1016/j.kint.2018.10.029DOI Listing

Using natural language processing to extract clinically useful information from Chinese electronic medical records.

Int J Med Inform 2019 Apr 7;124:6-12. Epub 2019 Jan 7.

Medical Genetic Institute of Henan Province, Henan Provincial People's Hospital, Henan Key Laboratory of Genetic Diseases and Functional Genomics, Henan Provincial People's Hospital of Henan University, Zhengzhou, Henan Province, PR China. Electronic address:

Aims: To develop a natural language processing (NLP)-based algorithm for extracting clinically useful information for patients with hepatocellular carcinoma (HCC) from Chinese electronic medical records (EMRs) and use these data for the assessment of HCC staging.

Materials And Methods: Clinical documents, including operation notes, radiology and pathology reports, of 92 HCC patients were collected from Chinese EMRs. We randomly grouped these patients into training (n = 60) and testing (n = 32) datasets. Read More

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http://dx.doi.org/10.1016/j.ijmedinf.2019.01.004DOI Listing

Toward liquid biopsies in cancer treatment: application of circulating tumor DNA.

APMIS 2019 Feb 19. Epub 2019 Feb 19.

Center for Genomic Medicine, Rigshospitalet, Copenhagen University, Copenhagen, Denmark.

Circulating tumor DNA (ctDNA) refers to the fraction of cell-free DNA in a patient's blood originating from tumor cells. Increased knowledge about tumor genomics, improvements in targeted therapies, and accompanying advances in DNA-sequencing technologies have increased the interest in using ctDNA as a minimally invasive tool in cancer diagnostics and treatment. Especially, early tumor detection including identification of minimal residual disease and stratification of adjuvant therapy are promising approaches. Read More

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http://dx.doi.org/10.1111/apm.12912DOI Listing
February 2019

Therapeutic implications of germline genetic findings in cancer.

Nat Rev Clin Oncol 2019 Feb 19. Epub 2019 Feb 19.

Cancer Division, Garvan Institute of Medical Research, Sydney, Australia.

Cancer is a genetic disease. To date, translational cancer genomics has focused largely on somatic alterations, driven by the desire to identify targets for personalized therapy. However, therapeutically relevant information is also latent within the germline genome. Read More

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http://dx.doi.org/10.1038/s41571-019-0179-3DOI Listing
February 2019

MicroRNA-196a is regulated by ER and is a prognostic biomarker in ER+ breast cancer.

Br J Cancer 2019 Feb 20. Epub 2019 Feb 20.

School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, QLD, Australia.

Background: MicroRNAs are potent post-transcriptional regulators involved in all hallmarks of cancer. Mir-196a is transcribed from two loci and has been implicated in a wide range of developmental and pathogenic processes, with targets including Hox, Fox, Cdk inhibitors and annexins. Genetic variants and altered expression of MIR196A are associated with risk and progression of multiple cancers including breast cancer, however little is known about the regulation of the genes encoding this miRNA, nor the impact of variants therein. Read More

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http://www.nature.com/articles/s41416-019-0395-8
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http://dx.doi.org/10.1038/s41416-019-0395-8DOI Listing
February 2019
1 Read

Dihydroartemisinin inhibits prostate cancer via JARID2/miR-7/miR-34a-dependent downregulation of Axl.

Oncogenesis 2019 Feb 19;8(3):14. Epub 2019 Feb 19.

International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town, South Africa.

Axl expression is deregulated in several cancer types, predicts poor overall patient survival and is linked to resistance to drug therapy. Here, we evaluated a library of natural compounds for inhibitors of Axl and identified dihydroartemisinin, the active principle of the anti-malarial drug artemisinin, as an Axl-inhibitor in prostate cancer. Dihydroartemisinin blocks Axl expression leading to apoptosis, decrease in cell proliferation, migration, and tumor development of prostate cancer cells. Read More

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http://dx.doi.org/10.1038/s41389-019-0122-6DOI Listing
February 2019

Analysis of mucosal melanoma whole-genome landscapes reveals clinically relevant genomic aberrations.

Clin Cancer Res 2019 Feb 19. Epub 2019 Feb 19.

Shanghai Key Laboratory of Stomatology, Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine

Purpose: Unlike advances in the genomics-driven precision treatment of cutaneous melanomas, the poor current understanding of the molecular basis of mucosal melanomas (MMs) has hindered such progress for MM patients. Thus, we sought to characterize the genomic landscape of MM to identify genomic alterations with prognostic and/or therapeutic implications.

Experimental Design: Whole-genome sequencing (WGS) was performed on 65 MM samples, including 63 paired tumor blood samples and 2 matched lymph node metastases, with a further ddPCR-based validation study of an independent MM cohort (n = 80). Read More

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http://clincancerres.aacrjournals.org/lookup/doi/10.1158/107
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http://dx.doi.org/10.1158/1078-0432.CCR-18-3442DOI Listing
February 2019
1 Read

Random and aligned electrospun PLGA nanofibers embedded in microfluidic chips for cancer cell isolation and integration with air foam technology for cell release.

J Nanobiotechnology 2019 Feb 19;17(1):31. Epub 2019 Feb 19.

Research Center for Applied Sciences, Academia Sinica, Taipei, 11529, Taiwan.

Background: Circulating tumor cells (CTCs) comprise the high metastatic potential population of cancer cells in the blood circulation of humans; they have become the established biomarkers for cancer diagnosis, individualized cancer therapy, and cancer development. Technologies for the isolation and recovery of CTCs can be powerful cancer diagnostic tools for liquid biopsies, allowing the identification of malignancies and guiding cancer treatments for precision medicine.

Methods: We have used an electrospinning process to prepare poly(lactic-co-glycolic acid) (PLGA) nanofibrous arrays in random or aligned orientations on glass slips. Read More

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http://dx.doi.org/10.1186/s12951-019-0466-2DOI Listing
February 2019

Leukocyte⁻Cancer Cell Fusion-Genesis of a Deadly Journey.

Cells 2019 Feb 18;8(2). Epub 2019 Feb 18.

Department of Dermatology and The Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520-8059, USA.

According to estimates from the International Agency for Research on Cancer, by the year 2030 there will be 22 million new cancer cases and 13 million deaths per year. The main cause of cancer mortality is not the primary tumor itself but metastasis to distant organs and tissues, yet the mechanisms of this process remain poorly understood. Leukocyte⁻cancer cell fusion and hybrid formation as an initiator of metastasis was proposed more than a century ago by the German pathologist Prof. Read More

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http://dx.doi.org/10.3390/cells8020170DOI Listing
February 2019

Identification of HIV gp41-specific antibodies that mediate killing of infected cells.

PLoS Pathog 2019 Feb 19;15(2):e1007572. Epub 2019 Feb 19.

Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle WA, United States of America.

Antibodies that mediate killing of HIV-infected cells through antibody-dependent cellular cytotoxicity (ADCC) have been implicated in protection from HIV infection and disease progression. Despite these observations, these types of HIV antibodies are understudied compared to neutralizing antibodies. Here we describe four monoclonal antibodies (mAbs) obtained from one individual that target the HIV transmembrane protein, gp41, and mediate ADCC activity. Read More

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http://dx.plos.org/10.1371/journal.ppat.1007572
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http://dx.doi.org/10.1371/journal.ppat.1007572DOI Listing
February 2019
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A component overlapping attribute clustering (COAC) algorithm for single-cell RNA sequencing data analysis and potential pathobiological implications.

PLoS Comput Biol 2019 Feb 19;15(2):e1006772. Epub 2019 Feb 19.

Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States of America.

Recent advances in next-generation sequencing and computational technologies have enabled routine analysis of large-scale single-cell ribonucleic acid sequencing (scRNA-seq) data. However, scRNA-seq technologies have suffered from several technical challenges, including low mean expression levels in most genes and higher frequencies of missing data than bulk population sequencing technologies. Identifying functional gene sets and their regulatory networks that link specific cell types to human diseases and therapeutics from scRNA-seq profiles are daunting tasks. Read More

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http://dx.doi.org/10.1371/journal.pcbi.1006772DOI Listing
February 2019

Identification of DNA mutations in gastric washes from gastric adenocarcinoma patients: possible implications for liquid biopsies and patient follow-up.

Int J Cancer 2019 Feb 18. Epub 2019 Feb 18.

Laboratory of Medical Genomics, A.C.Camargo Cancer Center, São Paulo, SP, Brazil.

Whereas cancer patients have benefited from liquid biopsies, the scenario for gastric adenocarcinoma (GAC) is still dismal. We used next-generation deep sequencing of TP53 - a highly mutated and informative gene in GAC - to assess mutations in tumor biopsies, plasma (PL) and stomach fluids (gastric wash - GW). We evaluated their potential to reveal tumor-derived mutations, useful for monitoring mutational dynamics at diagnosis, progression, and treatment. Read More

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http://dx.doi.org/10.1002/ijc.32217DOI Listing
February 2019

Lymphoma and Leukemia Cell Vulnerabilities and Resistance Identified by Compound Library Screens.

Methods Mol Biol 2019 ;1956:351-362

Department of Haematology, Center for Oncology and Haematology, University Hospital and University of Zurich, Zurich, Switzerland.

Response to anticancer agents is often restricted to subsets of patients. The recognition of factors underlying this heterogeneity and the identification of biomarkers associated with response to drugs would greatly improve the efficacy of drug treatment. Platforms that can comprehensively map drug response in high-throughput ex vivo provide a unique tool to identify associated biomarkers and provide hypotheses for mechanisms underlying variable response. Read More

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http://dx.doi.org/10.1007/978-1-4939-9151-8_17DOI Listing
January 2019

Protocols for CRISPR-Cas9 Screening in Lymphoma Cell Lines.

Methods Mol Biol 2019 ;1956:337-350

Lymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Genome-wide screens are a powerful technique to dissect the complex network of genes regulating diverse cellular phenotypes. The recent adaptation of the CRISPR-Cas9 system for genome engineering has revolutionized functional genomic screening. Here, we present protocols used to introduce Cas9 into human lymphoma cell lines, produce high-titer lentivirus of a genome-wide sgRNA library, transduce and culture cells during the screen, isolate genomic DNA, and prepare a custom library for next-generation sequencing. Read More

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http://dx.doi.org/10.1007/978-1-4939-9151-8_16DOI Listing
January 2019

Studying Cancer Heterogeneity by Single-Cell RNA Sequencing.

Methods Mol Biol 2019 ;1956:305-319

Anthropology & Human Genomics, Department of Biology II, Ludwig-Maximilians-University, Martinsried, Germany.

A major hurdle for the treatment of cancer is the incomplete understanding of its evolution through the course of its emergence, dispersal, and relapse. Genetic and epigenetic changes in combination with external cues and selective forces are the driving factors behind tumor heterogeneity. Understanding this variability within and across patients may partly explain the unpredictable outcomes of cancer treatments. Read More

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http://dx.doi.org/10.1007/978-1-4939-9151-8_14DOI Listing
January 2019

RNA Sequencing in B-Cell Lymphomas.

Methods Mol Biol 2019 ;1956:283-303

Institute of Pathology, University Hospital Giessen, Justus-Liebig-University Giessen, Giessen, Germany.

High-throughput mRNA sequencing (RNA-Seq) provides both qualitative and quantitative evaluation of the transcriptome. This method uses complementary DNA (cDNA) to generate several millions of short sequence reads that are aligned to a reference genome allowing the comprehensive characterization of the transcripts in a cell. RNA-Seq has a wide variety of applications which lead to a pervasive adoption of this method well beyond the genomics community and a deployment of this technique as a standard part of the toolkit applied in life sciences. Read More

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http://dx.doi.org/10.1007/978-1-4939-9151-8_13DOI Listing
January 2019

Inherited Interleukin 2-Inducible T-Cell (ITK) Kinase Deficiency in Siblings With Epidermodysplasia Verruciformis and Hodgkin Lymphoma.

Clin Infect Dis 2019 Feb 19. Epub 2019 Feb 19.

Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, and Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania.

Biallelic mutations in the ITK gene cause a T-cell primary immunodeficiency with Epstein-Barr virus (EBV)-lymphoproliferative disorders. We describe a novel association of a homozygous ITK mutation with β-human papillomavirus (HPV)-positive epidermodysplasia verruciformis. Thus, loss of function in ITK can result in broad dysregulation of T-cell responses to oncogenic viruses, including β-HPV and EBV. Read More

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https://academic.oup.com/cid/advance-article/doi/10.1093/cid
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http://dx.doi.org/10.1093/cid/ciy942DOI Listing
February 2019
3 Reads

De-escalated therapy for HR+/HER2+ breast cancer patients with Ki67 response after 2 weeks letrozole: results of the PerELISA neoadjuvant study.

Ann Oncol 2019 Feb 18. Epub 2019 Feb 18.

Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy.

Background: In HER2+ breast cancers, neoadjuvant trials of chemotherapy plus anti-HER2 treatment consistently showed lower pathologic complete response (pCR) rates in hormone receptor (HR) positive vs negative tumors. The PerELISA study was aimed to evaluate the efficacy of a de-escalated, chemotherapy-free neoadjuvant regimen in HR+/HER2+ breast cancer patients selected on the basis of Ki67 inhibition after 2-weeks letrozole.

Patients And Methods: PerELISA is a phase II, multicentric study for postmenopausal patients with HR+/HER2+ operable breast cancer. Read More

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http://dx.doi.org/10.1093/annonc/mdz055DOI Listing
February 2019

Multi-omic measurements of heterogeneity in HeLa cells across laboratories.

Nat Biotechnol 2019 Feb 18. Epub 2019 Feb 18.

Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.

Reproducibility in research can be compromised by both biological and technical variation, but most of the focus is on removing the latter. Here we investigate the effects of biological variation in HeLa cell lines using a systems-wide approach. We determine the degree of molecular and phenotypic variability across 14 stock HeLa samples from 13 international laboratories. Read More

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http://www.nature.com/articles/s41587-019-0037-y
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http://dx.doi.org/10.1038/s41587-019-0037-yDOI Listing
February 2019
1 Read

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Authors:
Anne E Justice Tugce Karaderi Heather M Highland Kristin L Young Mariaelisa Graff Yingchang Lu Valérie Turcot Paul L Auer Rebecca S Fine Xiuqing Guo Claudia Schurmann Adelheid Lempradl Eirini Marouli Anubha Mahajan Thomas W Winkler Adam E Locke Carolina Medina-Gomez Tõnu Esko Sailaja Vedantam Ayush Giri Ken Sin Lo Tamuno Alfred Poorva Mudgal Maggie C Y Ng Nancy L Heard-Costa Mary F Feitosa Alisa K Manning Sara M Willems Suthesh Sivapalaratnam Goncalo Abecasis Dewan S Alam Matthew Allison Philippe Amouyel Zorayr Arzumanyan Beverley Balkau Lisa Bastarache Sven Bergmann Lawrence F Bielak Matthias Blüher Michael Boehnke Heiner Boeing Eric Boerwinkle Carsten A Böger Jette Bork-Jensen Erwin P Bottinger Donald W Bowden Ivan Brandslund Linda Broer Amber A Burt Adam S Butterworth Mark J Caulfield Giancarlo Cesana John C Chambers Daniel I Chasman Yii-Der Ida Chen Rajiv Chowdhury Cramer Christensen Audrey Y Chu Francis S Collins James P Cook Amanda J Cox David S Crosslin John Danesh Paul I W de Bakker Simon de Denus Renée de Mutsert George Dedoussis Ellen W Demerath Joe G Dennis Josh C Denny Emanuele Di Angelantonio Marcus Dörr Fotios Drenos Marie-Pierre Dubé Alison M Dunning Douglas F Easton Paul Elliott Evangelos Evangelou Aliki-Eleni Farmaki Shuang Feng Ele Ferrannini Jean Ferrieres Jose C Florez Myriam Fornage Caroline S Fox Paul W Franks Nele Friedrich Wei Gan Ilaria Gandin Paolo Gasparini Vilmantas Giedraitis Giorgia Girotto Mathias Gorski Harald Grallert Niels Grarup Megan L Grove Stefan Gustafsson Jeff Haessler Torben Hansen Andrew T Hattersley Caroline Hayward Iris M Heid Oddgeir L Holmen G Kees Hovingh Joanna M M Howson Yao Hu Yi-Jen Hung Kristian Hveem M Arfan Ikram Erik Ingelsson Anne U Jackson Gail P Jarvik Yucheng Jia Torben Jørgensen Pekka Jousilahti Johanne M Justesen Bratati Kahali Maria Karaleftheri Sharon L R Kardia Fredrik Karpe Frank Kee Hidetoshi Kitajima Pirjo Komulainen Jaspal S Kooner Peter Kovacs Bernhard K Krämer Kari Kuulasmaa Johanna Kuusisto Markku Laakso Timo A Lakka David Lamparter Leslie A Lange Claudia Langenberg Eric B Larson Nanette R Lee Wen-Jane Lee Terho Lehtimäki Cora E Lewis Huaixing Li Jin Li Ruifang Li-Gao Li-An Lin Xu Lin Lars Lind Jaana Lindström Allan Linneberg Ching-Ti Liu Dajiang J Liu Jian'an Luan Leo-Pekka Lyytikäinen Stuart MacGregor Reedik Mägi Satu Männistö Gaëlle Marenne Jonathan Marten Nicholas G D Masca Mark I McCarthy Karina Meidtner Evelin Mihailov Leena Moilanen Marie Moitry Dennis O Mook-Kanamori Anna Morgan Andrew P Morris Martina Müller-Nurasyid Patricia B Munroe Narisu Narisu Christopher P Nelson Matt Neville Ioanna Ntalla Jeffrey R O'Connell Katharine R Owen Oluf Pedersen Gina M Peloso Craig E Pennell Markus Perola James A Perry John R B Perry Tune H Pers Ailith Ewing Ozren Polasek Olli T Raitakari Asif Rasheed Chelsea K Raulerson Rainer Rauramaa Dermot F Reilly Alex P Reiner Paul M Ridker Manuel A Rivas Neil R Robertson Antonietta Robino Igor Rudan Katherine S Ruth Danish Saleheen Veikko Salomaa Nilesh J Samani Pamela J Schreiner Matthias B Schulze Robert A Scott Marcelo Segura-Lepe Xueling Sim Andrew J Slater Kerrin S Small Blair H Smith Jennifer A Smith Lorraine Southam Timothy D Spector Elizabeth K Speliotes Kari Stefansson Valgerdur Steinthorsdottir Kathleen E Stirrups Konstantin Strauch Heather M Stringham Michael Stumvoll Liang Sun Praveen Surendran Karin M A Swart Jean-Claude Tardif Kent D Taylor Alexander Teumer Deborah J Thompson Gudmar Thorleifsson Unnur Thorsteinsdottir Betina H Thuesen Anke Tönjes Mina Torres Emmanouil Tsafantakis Jaakko Tuomilehto André G Uitterlinden Matti Uusitupa Cornelia M van Duijn Mauno Vanhala Rohit Varma Sita H Vermeulen Henrik Vestergaard Veronique Vitart Thomas F Vogt Dragana Vuckovic Lynne E Wagenknecht Mark Walker Lars Wallentin Feijie Wang Carol A Wang Shuai Wang Nicholas J Wareham Helen R Warren Dawn M Waterworth Jennifer Wessel Harvey D White Cristen J Willer James G Wilson Andrew R Wood Ying Wu Hanieh Yaghootkar Jie Yao Laura M Yerges-Armstrong Robin Young Eleftheria Zeggini Xiaowei Zhan Weihua Zhang Jing Hua Zhao Wei Zhao He Zheng Wei Zhou M Carola Zillikens Fernando Rivadeneira Ingrid B Borecki J Andrew Pospisilik Panos Deloukas Timothy M Frayling Guillaume Lettre Karen L Mohlke Jerome I Rotter Zoltán Kutalik Joel N Hirschhorn L Adrienne Cupples Ruth J F Loos Kari E North Cecilia M Lindgren

Nat Genet 2019 Feb 18. Epub 2019 Feb 18.

Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Read More

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http://dx.doi.org/10.1038/s41588-018-0334-2DOI Listing
February 2019
29.352 Impact Factor

The DNA modification N6-methyl-2'-deoxyadenosine (m6dA) drives activity-induced gene expression and is required for fear extinction.

Nat Neurosci 2019 Feb 18. Epub 2019 Feb 18.

Cognitive Neuroepigenetics Laboratory, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.

DNA modification is known to regulate experience-dependent gene expression. However, beyond cytosine methylation and its oxidated derivatives, very little is known about the functional importance of chemical modifications on other nucleobases in the brain. Here we report that in adult mice trained in fear extinction, the DNA modification N6-methyl-2'-deoxyadenosine (m6dA) accumulates along promoters and coding sequences in activated prefrontal cortical neurons. Read More

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http://dx.doi.org/10.1038/s41593-019-0339-xDOI Listing
February 2019

H19 potentiates let-7 family expression through reducing PTBP1 binding to their precursors in cholestasis.

Cell Death Dis 2019 Feb 18;10(3):168. Epub 2019 Feb 18.

Veterans Affairs Connecticut Healthcare System, West Haven, CT, 06516, USA.

Cholestasis induces the hepatic long non-coding RNA H19, which promotes the progression of cholestatic liver fibrosis. However, microRNAs that are dysregulated by H19 during cholestasis remain elusive. Using miRNA-sequencing analysis followed by qPCR validation, we identified marked upregulation of eight members of the let-7 family in cholestatic livers by bile duct ligation (BDL) and H19 overexpression. Read More

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http://dx.doi.org/10.1038/s41419-019-1423-6DOI Listing
February 2019

BAP1 haploinsufficiency predicts a distinct immunogenic class of malignant peritoneal mesothelioma.

Genome Med 2019 Feb 18;11(1). Epub 2019 Feb 18.

Vancouver Prostate Centre, 2660 Oak St, Vancouver, BC, V6H 3Z6, Canada.

Background: Malignant peritoneal mesothelioma (PeM) is a rare and fatal cancer that originates from the peritoneal lining of the abdomen. Standard treatment of PeM is limited to cytoreductive surgery and/or chemotherapy, and no effective targeted therapies for PeM exist. Some immune checkpoint inhibitor studies of mesothelioma have found positivity to be associated with a worse prognosis. Read More

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http://dx.doi.org/10.1186/s13073-019-0620-3DOI Listing
February 2019

Metagenomic and metatranscriptomic analysis of human prostate microbiota from patients with prostate cancer.

BMC Genomics 2019 Feb 18;20(1):146. Epub 2019 Feb 18.

Vancouver Prostate Centre, Vancouver, Canada.

Background: Prostate cancer (PCa) is the most common malignant neoplasm among men in many countries. Since most precancerous and cancerous tissues show signs of inflammation, chronic bacterial prostatitis has been hypothesized to be a possible etiology. However, establishing a causal relationship between microbial inflammation and PCa requires a comprehensive analysis of the prostate microbiome. Read More

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http://dx.doi.org/10.1186/s12864-019-5457-zDOI Listing
February 2019
1 Read

Hepatic differentiation of human pluripotent stem cells by developmental stage-related metabolomics products.

Differentiation 2019 Jan 28;105:54-70. Epub 2019 Jan 28.

Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Diabetes Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Irwin S. and Sylvia Chanin Institute for Cancer Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address:

Endogenous cell signals regulate tissue homeostasis and are significant for directing the fate of stem cells. During liver development, cytokines released from various cell types are critical for stem/progenitor cell differentiation and lineage expansions. To determine mechanisms in these stage-specific lineage interactions, we modeled potential effects of soluble signals derived from immortalized human fetal liver parenchymal cells on stem cells, including embryonic and induced pluripotent stem cells. Read More

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http://dx.doi.org/10.1016/j.diff.2019.01.005DOI Listing
January 2019

Dynamic evolution of clonal composition and neoantigen landscape in recurrent metastatic melanoma with a rare combination of driver mutations.

J Invest Dermatol 2019 Feb 15. Epub 2019 Feb 15.

Institut de Génétique et de Biologie Moléculaire et Cellulaire, UMR7104 CNRS; U1258 INSERM; Université de Strasbourg, Department of Functional Genomics and Cancer, 1 Rue Laurent Fries, 67404 Illkirch Cédex. France. Electronic address:

In melanoma, initiating oncogenic mutations in BRAF or NRAS are detected in premalignant lesions that accumulate additional mutations and genomic instability as the tumour evolves to the metastatic state. Here we investigate evolution of clonal composition and neoantigen landscape in an atypical melanoma displaying recurrent cutaneous lesions over a 6-year period without development of extra-cutaneous metastases. Whole exome sequencing of 4 cutaneous lesions taken over the 6-year period identified a collection of single nucleotide variants (SNVs) and small insertions and deletions (Indels) shared amongst all tumours along with progressive selection of subclones displaying fewer SNVs. Read More

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http://dx.doi.org/10.1016/j.jid.2019.01.027DOI Listing
February 2019

Endometriosis-associated ovarian cancer: What have we learned so far?

Clin Chim Acta 2019 Feb 15. Epub 2019 Feb 15.

Division of Laboratory Medicine, Asia University Hospital, Asia University, Taichung, Taiwan; Deparment of Food Nutrition and Health Biotechnology, Asia University, Taichung, Taiwan; Deparment of Post-Baccalaureate Veterinary Medicine, Asia University, Taichung, Taiwan; Deparment of Nursing, Asia University, Taichung, Taiwan. Electronic address:

Endometriosis is defined as the presence of ectopic endometrial tissue outside of the uterine cavity, most commonly in the ovaries and peritoneum. It is a complex disease that is influenced by multiple factors. It is also a common gynecological disorder and affects approximately 10-15% of all women of reproductive age. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00098981193006
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http://dx.doi.org/10.1016/j.cca.2019.02.016DOI Listing
February 2019
4 Reads

A novel approach to offering additional genomic findings-A protocol to test a two-step approach in the healthcare system.

J Genet Couns 2019 Feb 18. Epub 2019 Feb 18.

Melbourne Genomics Health Alliance, Melbourne, Australia.

Internationally, the practice of offering additional findings (AFs) when undertaking a clinically indicated genomic test differs. In the USA, the recommendation is to include analysis for AFs alongside diagnostic analysis, unless a patient opts-out, whereas European and Canadian guidelines recommend opt-in models. These guidelines all consider the offer of AFs as an activity concurrent with the offer of diagnostic testing. Read More

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http://dx.doi.org/10.1002/jgc4.1102DOI Listing
February 2019

Gene and protein expression profiles of JAK-STAT signalling pathway in the developing brain of the Ts1Cje Down syndrome mouse model.

Int J Neurosci 2019 Feb 18:1-13. Epub 2019 Feb 18.

a Genetics & Regenerative Medicine Research Centre (GRMRC), Faculty of Medicine and Health Sciences , Universiti Putra Malaysia , Selangor , Malaysia .

Aims: The JAK-STAT signalling pathway is one of the key regulators of pro-gliogenesis process during brain development. Down syndrome (DS) individuals, as well as DS mouse models, exhibit an increased number of astrocytes, suggesting an imbalance of neurogenic-to-gliogenic shift attributed to dysregulated JAK-STAT signalling pathway. The gene and protein expression profiles of JAK-STAT pathway members have not been characterised in the DS models. Read More

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http://dx.doi.org/10.1080/00207454.2019.1580280DOI Listing
February 2019

Inhibition of histone methyltransferase DOT1L silences ERα gene and blocks proliferation of antiestrogen-resistant breast cancer cells.

Sci Adv 2019 Feb 6;5(2):eaav5590. Epub 2019 Feb 6.

Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry, "Scuola Medica Salernitana", University of Salerno, Baronissi, SA, Italy.

Breast cancer (BC) resistance to endocrine therapy results from constitutively active or aberrant estrogen receptor α (ERα) signaling, and ways to block ERα pathway in these tumors are sought after. We identified the H3K79 methyltransferase DOT1L as a novel cofactor of ERα in BC cell chromatin, where the two proteins colocalize to regulate estrogen target gene transcription. DOT1L blockade reduces proliferation of hormone-responsive BC cells in vivo and in vitro, consequent to cell cycle arrest and apoptotic cell death, with widespread effects on ER-dependent gene transcription, including ERα and FOXA1 gene silencing. Read More

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http://dx.doi.org/10.1126/sciadv.aav5590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365116PMC
February 2019

Targeting androgen receptor-independent pathways in therapy-resistant prostate cancer.

Asian J Urol 2019 Jan 28;6(1):91-98. Epub 2018 Nov 28.

Department of Pathology, Duke University School of Medicine, Durham, NC, USA.

Since androgen receptor (AR) signaling is critically required for the development of prostate cancer (PCa), targeting AR axis has been the standard treatment of choice for advanced and metastatic PCa. Unfortunately, although the tumor initially responds to the therapy, treatment resistance eventually develops and the disease will progress. It is therefore imperative to identify the mechanisms of therapeutic resistance and novel molecular targets that are independent of AR signaling. Read More

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http://dx.doi.org/10.1016/j.ajur.2018.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363598PMC
January 2019
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Systems proteogenomics for precision oncology.

Oncotarget 2019 Jan 22;10(7):692-693. Epub 2019 Jan 22.

Frederick Klauschen: Systems Pathology Group, Institute of Pathology, Charité Universitätsmedizin Berlin, Germany; German Cancer Consortium, Berlin Partner Site and German Cancer Research Center, Heidelberg, Germany.

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http://dx.doi.org/10.18632/oncotarget.26601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366822PMC
January 2019

Retinoblastoma mutation predicts poor outcomes in advanced non small cell lung cancer.

Cancer Med 2019 Feb 17. Epub 2019 Feb 17.

Department of Hematology and Oncology, Case Western Reserve University, University Hospitals Seidman Cancer Center, Cleveland, Ohio.

The retinoblastoma gene (RB1) encodes the retinoblastoma (RB) pocket protein that plays an important role in cell cycle progression. Here we determine the frequency and prognostic significance of RB1 mutation in non small cell lung cancer (NSCLC), restricting inclusion to Stage III and IV patients with linked genomic and clinical data. The primary outcome was median overall survival (OS). Read More

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http://dx.doi.org/10.1002/cam4.2023DOI Listing
February 2019

Serine Metabolism Supports Macrophage IL-1β Production.

Cell Metab 2019 Feb 7. Epub 2019 Feb 7.

Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. Electronic address:

Serine is a substrate for nucleotide, NADPH, and glutathione (GSH) synthesis. Previous studies in cancer cells and lymphocytes have shown that serine-dependent one-carbon units are necessary for nucleotide production to support proliferation. Presently, it is unknown whether serine metabolism impacts the function of non-proliferative cells, such as inflammatory macrophages. Read More

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http://dx.doi.org/10.1016/j.cmet.2019.01.014DOI Listing
February 2019
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Hypomorphic Mutations in TONSL Cause SPONASTRIME Dysplasia.

Am J Hum Genet 2019 Feb 8. Epub 2019 Feb 8.

Department of Orthopaedic Surgery, Seoul National University College of Medicine, Seoul 03080, Republic of Korea. Electronic address:

SPONASTRIME dysplasia is a rare, recessive skeletal dysplasia characterized by short stature, facial dysmorphism, and aberrant radiographic findings of the spine and long bone metaphysis. No causative genetic alterations for SPONASTRIME dysplasia have yet been determined. Using whole-exome sequencing (WES), we identified bi-allelic TONSL mutations in 10 of 13 individuals with SPONASTRIME dysplasia. Read More

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http://dx.doi.org/10.1016/j.ajhg.2019.01.009DOI Listing
February 2019

Bi-allelic Variants in TONSL Cause SPONASTRIME Dysplasia and a Spectrum of Skeletal Dysplasia Phenotypes.

Am J Hum Genet 2019 Feb 11. Epub 2019 Feb 11.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Texas Children's Hospital, Houston, TX 77030, USA. Electronic address:

SPONASTRIME dysplasia is an autosomal-recessive spondyloepimetaphyseal dysplasia characterized by spine (spondylar) abnormalities, midface hypoplasia with a depressed nasal bridge, metaphyseal striations, and disproportionate short stature. Scoliosis, coxa vara, childhood cataracts, short dental roots, and hypogammaglobulinemia have also been reported in this disorder. Although an autosomal-recessive inheritance pattern has been hypothesized, pathogenic variants in a specific gene have not been discovered in individuals with SPONASTRIME dysplasia. Read More

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http://dx.doi.org/10.1016/j.ajhg.2019.01.007DOI Listing
February 2019

Enhanced type I interferon gene signature in primary antiphospholipid syndrome: Association with earlier disease onset and preeclampsia.

Autoimmun Rev 2019 Feb 14. Epub 2019 Feb 14.

Rheumatology Division, Faculdade de Medicina da Universidade de São Paulo (USP), Brazil.

Objective: Recently, two studies demonstrated that a relevant percentage of primary antiphospholipid syndrome (PAPS) patients had an upregulation of interferon (IFN) genes. However, 20%-28% of these patients had anti-dsDNA, a highly specific systemic lupus erythematosus (SLE) autoantibody. This study aimed to determine the prevalence of the type I IFN signature in the peripheral blood mononuclear cells of PAPS patients without specific SLE autoantibodies and search for its clinical associations. Read More

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http://dx.doi.org/10.1016/j.autrev.2018.11.004DOI Listing
February 2019

Quantitative label-free mass spectrometry using contralateral and adjacent breast tissues reveal differentially expressed proteins and their predicted impacts on pathways and cellular functions in breast cancer.

J Proteomics 2019 Feb 14. Epub 2019 Feb 14.

Genetics Department, Federal University of Parana, Curitiba, Brazil. Electronic address:

Proteins play an essential role in the biological processes associated with cancer. Their altered expression levels can deregulate critical cellular pathways and interactive networks. In this study, the mass spectrometry-based label-free quantification followed by functional annotation was performed to investigate the most significant deregulated proteins among tissues of primary breast tumor (PT) and axillary metastatic lymph node (LN) and corresponding non-tumor tissues contralateral (NCT) and adjacent (ANT) from patients diagnosed with invasive ductal carcinoma. Read More

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http://dx.doi.org/10.1016/j.jprot.2019.02.007DOI Listing
February 2019
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Deep-Resp-Forest: A deep forest model to predict anti-cancer drug response.

Methods 2019 Feb 14. Epub 2019 Feb 14.

Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu, China. Electronic address:

The identification of therapeutic biomarkers predictive of drug response is crucial in personalized medicine. A number of computational models to predict response of anti-cancer drugs have been developed as the establishment of several pharmacogenomics screening databases. In our study, we proposed a deep cascaded forest model, Deep-Resp-Forest, to classify the anti-cancer drug response as "sensitive" or "resistant". Read More

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http://dx.doi.org/10.1016/j.ymeth.2019.02.009DOI Listing
February 2019

A SUV39H1-low chromatin state characterises and promotes migratory properties of cervical cancer cells.

Exp Cell Res 2019 Feb 14. Epub 2019 Feb 14.

National Centre for Biological Sciences, Tata Institute of Fundamental Research, GKVK-UAS, Bangalore, India. Electronic address:

Metastatic progression is a major cause of mortality in cervical cancers, but factors regulating migratory and pre-metastatic cell populations remain poorly understood. Here, we sought to assess whether a SUV39H1-low chromatin state promotes migratory cell populations in cervical cancers, using meta-analysis of data from The Cancer Genome Atlas (TCGA), immunohistochemistry, genomics and functional assays. Cervical cancer cells sorted based on migratory ability in vitro have low levels of SUV39H1 protein, and SUV39H1 knockdown in vitro enhanced cervical cancer cell migration. Read More

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http://dx.doi.org/10.1016/j.yexcr.2019.02.010DOI Listing
February 2019

Feasibility of Qualitative Testing of BCR-ABL and JAK2 V617F in Suspected Myeloproliperative Neoplasm (MPN) Using RT-PCR Reversed Dot Blot Hybridization (RT-PCR RDB).

Clin Lymphoma Myeloma Leuk 2019 Jan 19. Epub 2019 Jan 19.

Stem Cell and Cancer Institute, Jakarta, Indonesia; Kalbe Genomics Laboratory, Jakarta, Indonesia.

Background: Defining the presence of BCR-ABL transcript in suspected myeloproliferative neoplasm is essential in establishing chronic myeloid leukemia. In the absence of BCR-ABL, the conventional diagnostic algorithm recommends JAK2 V617F mutation testing to support diagnosis of other MPN diseases such as polycythemia vera, essential thrombocythemia, and primary myelofibrosis. In certain cases of thrombocythemia, simultaneous upfront testing of both BCR-ABL and JAK2 may be desirable. Read More

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http://dx.doi.org/10.1016/j.clml.2019.01.005DOI Listing
January 2019
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Long-term correction of hemophilia B using adenoviral delivery of CRISPR/Cas9.

J Control Release 2019 Feb 13;298:128-141. Epub 2019 Feb 13.

Cancer Biology Division, Department of Radiation Oncology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8224, St. Louis, MO 63110, USA; Department of Radiation Oncology, Biologic Therapeutics Center, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8224, St. Louis, MO 63110, USA. Electronic address:

Hemophilia B (HB) is a life-threatening inherited disease caused by mutations in the FIX gene, leading to reduced protein function and abnormal blood clotting. Due to its monogenic nature, HB is one of the primary targets for gene therapy. Indeed, successful correction of HB has been shown in clinical trials using gene therapy approaches. Read More

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http://dx.doi.org/10.1016/j.jconrel.2019.02.009DOI Listing
February 2019
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Proteomic and genomic profiling of pancreatic cancer.

Cell Biol Toxicol 2019 Feb 15. Epub 2019 Feb 15.

Department of Surgery, Clinical Sciences Lund, Skåne University Hospital, Lund University, SE-221 85, Lund, Sweden.

Pancreatic cancer remains the most fatal human tumor type. The aggressive tumor biology coupled with the lack of early detection strategies and effective treatment are major reasons for the poor survival rate. Collaborative research efforts have been devoted to understand pancreatic cancer at the molecular level. Read More

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http://dx.doi.org/10.1007/s10565-019-09465-9DOI Listing
February 2019
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Functional high-throughput screening reveals miR-323a-5p and miR-342-5p as new tumor-suppressive microRNA for neuroblastoma.

Cell Mol Life Sci 2019 Feb 15. Epub 2019 Feb 15.

Group of Translational Research in Child and Adolescent Cancer, Vall d'Hebron Research Institute (VHIR)-Universitat Autònoma de Barcelona (UAB), Passeig Vall d'Hebron 119-129, Collserola Building. Lab 207, 08035, Barcelona, Spain.

Current therapies for most non-infectious diseases are directed at or affect functionality of the human translated genome, barely 2% of all genetic information. By contrast, the therapeutic potential of targeting the transcriptome, ~ 70% of the genome, remains largely unexplored. RNA therapeutics is an emerging field that widens the range of druggable targets and includes elements such as microRNA. Read More

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http://dx.doi.org/10.1007/s00018-019-03041-4DOI Listing
February 2019
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Imprint of parity and age at first pregnancy on the genomic landscape of subsequent breast cancer.

Breast Cancer Res 2019 Feb 15;21(1):25. Epub 2019 Feb 15.

Breast Cancer Translational Research Laboratory J.-C. Heuson, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Brussels, Belgium.

Background: Although parity and age at first pregnancy are among the most known extrinsic factors that modulate breast cancer risk, their impact on the biology of subsequent breast cancer has never been explored in depth. Recent data suggest that pregnancy-induced tumor protection is different according to breast cancer subtypes, with parity and young age at first pregnancy being associated with a marked reduction in the risk of developing luminal subtype but not triple negative breast cancer. In this study, we investigated the imprint of parity and age at first pregnancy on the pattern of somatic mutations, somatic copy number alterations, transcriptomic profiles, and tumor immune microenvironment by assessing tumor-infiltrating lymphocytes (TILs) levels of subsequent breast cancer. Read More

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http://dx.doi.org/10.1186/s13058-019-1111-6DOI Listing
February 2019
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Design of peptide nucleic acid probes on plasmonic gold nanorods for detection of circulating tumor DNA point mutations.

Biosens Bioelectron 2019 Jan 29;130:236-244. Epub 2019 Jan 29.

Thayer School of Engineering, Dartmouth College, 14 Engineering Drive, Hanover, NH 03755, USA; Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, NH 03766, USA. Electronic address:

Here we present a gold nanorod-based platform for the sequence-specific detection of circulating tumor DNA (ctDNA) point mutations without the need for amplification or fluorescence labeling. Peptide nucleic acid probes complimentary to the G12V mutation in the KRAS gene were conjugated to gold nanorods, and the localized surface plasmon resonance absorbance through the sample was measured after exposure to synthetic ctDNA at various concentrations. Each step of the reaction was thoroughly controlled, starting from reagent concentrations and including conjugation, sonication, and incubation time. Read More

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http://dx.doi.org/10.1016/j.bios.2019.01.045DOI Listing
January 2019