41,830 results match your criteria Cancer Genomics & Proteomics[Journal]


In Situ Modification of Tissue Stem and Progenitor Cell Genomes.

Cell Rep 2019 Apr;27(4):1254-1264.e7

Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Paul F. Glenn Center for the Biology of Aging, Harvard Medical School, Boston, MA 02115, USA; Joslin Diabetes Center, Boston, MA 02215, USA. Electronic address:

In vivo delivery of genome-modifying enzymes holds significant promise for therapeutic applications and functional genetic screening. Delivery to endogenous tissue stem cells, which provide an enduring source of cell replacement during homeostasis and regeneration, is of particular interest. Here, we use a sensitive Cre/lox fluorescent reporter system to test the efficiency of genome modification following in vivo transduction by adeno-associated viruses (AAVs) in tissue stem and progenitor cells. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2019.03.105DOI Listing

Heterozygosity mapping for human dominant trait variants.

Hum Mutat 2019 Apr 24. Epub 2019 Apr 24.

Laboratory of Statistical Genetics, Rockefeller University, New York, New York.

Homozygosity mapping is a well-known technique to identify runs of homozygous variants that are likely to harbor genes responsible for autosomal recessive disease, but a comparable method for autosomal dominant traits has been lacking. We developed an approach to map dominant disease genes based on heterozygosity frequencies of sequence variants in the immediate vicinity of a dominant trait. We demonstrate through theoretical analysis that DNA variants surrounding an inherited dominant disease variant tend to have increased heterozygosity compared with variants elsewhere in the genome. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.23765DOI Listing

Extending expressed RNA genomics from surgical decision making for cytologically indeterminate thyroid nodules to targeting therapies for metastatic thyroid cancer.

Cancer Cytopathol 2019 Apr 24. Epub 2019 Apr 24.

Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.

View Article

Download full-text PDF

Source
https://onlinelibrary.wiley.com/doi/abs/10.1002/cncy.22132
Publisher Site
http://dx.doi.org/10.1002/cncy.22132DOI Listing
April 2019
1 Read

Kallikarein-related peptidase 3 common genetic variant and the risk of prostate cancer.

J Cell Biochem 2019 Apr 24. Epub 2019 Apr 24.

Medical Genomics Research Center, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

Kallikarein-related peptidase 3 (KLK3) gene polymorphisms seem to play a role in susceptibility to prostate cancer (PC). The purpose of this study was to investigate the association between rs2735839 polymorphism of KLK3 gene and risk of PC in an Iranian population. In this case-control study, rs2735839 was genotyped in 532 patients with PC and 602 controls with benign prostate hyperplasia (BPH) using polymerase chain reaction-restriction fragment length polymorphism assay. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcb.28743DOI Listing

[Comprehensive analysis of the aberrantly expressed profiles of lncRNAs, miRNAs and the regulation network of the associated ceRNAs in clear cell renal cell carcinoma].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2019 Apr;36(2):267-273

Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, P.R.China;Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, Chengdu 610041,

To evaluate the differential expression profiles of the lncRNAs, miRNAs, mRNAs and ceRNAs, and their implication in the prognosis in clear cell renal cell carcinoma (CCRCC), the large sample genomics analysis technologies were used in this study. The RNA and miRNA sequencing data of CCRCC were obtained from The Cancer Genome Atlas (TCGA) database, and R software was used for gene expression analysis and survival analysis. Cytoscape software was used to construct the ceRNA network. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.7507/1001-5515.201801057DOI Listing

Estrogen receptor variants in ER-positive basal-type breast cancers responding to therapy like ER-negative breast cancers.

NPJ Breast Cancer 2019 18;5:15. Epub 2019 Apr 18.

Nashville Breast Center, Nashville, TN USA.

Immunohistochemically ER-positive HER2-negative (ER+HER2-) breast cancers are classified clinically as Luminal-type. We showed previously that molecular subtyping using the 80-gene signature (80-GS) reclassified a subset of ER+HER2- tumors to molecular Basal-type. We report here that molecular reclassification is associated with expression of dominant-negative ER variants and evaluate response to neoadjuvant therapy and outcome in the prospective neoadjuvant NBRST study (NCT01479101). Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41523-019-0109-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472385PMC

Profile of HBV Integration in the Plasma DNA of Hepatocellular Carcinoma Patients.

Curr Genomics 2019 Jan;20(1):61-68

1Jining Medical University, Jining, Shandong272067, China; 2Collaborative Innovation Center for Birth Defect Research and Transformation of Shandong Province, Jining Medical University, Jining, Shandong272067, China; 3Southern University of Science and Technology, Shenzhen518055, China; 4Shenzhen Institute of Transfusion Medicine, Shenzhen Blood Center, Shenzhen518002, China; 5Center for Data Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA19104, USA; 6BGI College, University of Chinese Academy of Sciences, Shenzhen518083, China.

Background: Hepatitis B Viral (HBV) infection is one of the major causes of Hepatocellular Carcinoma (HCC). Mounting evidence had provided that the HBV integration might be a critical con-tributor of HCC carcinogenesis.

Objective And Methods: To explore the profile of HBV integration in the plasma DNA, the method of next-generation sequencing, HBV capture and bioinformatics had been employed to screen for HBV in-tegration sites in the plasma samples. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.2174/1389202919666181002144336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446477PMC
January 2019

Integrated Transcriptome Analysis of microRNA and mRNA in Mouse Skin Derived Precursors (SKPs) and SKP Derived Fibroblast (SFBs) by RNA-Seq.

Curr Genomics 2019 Jan;20(1):49-60

1Department of Dermatology, West China Hospital, Sichuan University, Chengdu610041, China; 2Department of Dermatology, Sichuan Academy of Science & Sichuan Provincial People's Hospital, University of Electronic Science and Technology, Chengdu610072, China.

Background: Skin-derived precursors (SKPs) display the characteristics of self-renewal and multilineage differentiation.

Objective: The study aimed to explore the molecular mechanisms of mouse SKPs differentiation into SKP-derived fibroblasts (SFBs).

Methods: We compared the microRNA (miRNA) profile in mouse SKPs and SFBs by RNA sequenc-ing. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.2174/1389202919666181012145416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446482PMC
January 2019
1 Read

Prostate Cancer Gene Regulatory Network Inferred from RNA-Seq Data.

Curr Genomics 2019 Jan;20(1):38-48

1School of Pharmacy, Queen's University Belfast, Belfast, BT9 7BL, UK; 2Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, MA02115, USA; 3Department of Mechatronics and Biomedical Computer Science, University for Health Sciences, Medical Informatics and Technology, 6060 Hall in Tirol, Austria; 4College of Computer and Control Engineering, Nankai University, Tianjin, China; 5Institute for Intelligent Production, Faculty for Management, University of Applied Sciences Upper Austria, Steyr, Austria; 6Department of Signal Processing, Predictive Medicine and Data Analytics Laboratory, Tampere University of Technology, Tampere33720, Finland; 7Institute of Biosciences and Medical Technology, Tampere, Finland.

Background: Cancer is a complex disease with a lucid etiology and in understanding the causation, we need to appreciate this complexity.

Objective: Here we are aiming to gain insights into the genetic associations of prostate cancer through a network-based systems approach using the BC3Net algorithm.

Methods: Specifically, we infer a prostate cancer Gene Regulatory Network (GRN) from a large-scale gene expression data set of 333 patient RNA-seq profiles obtained from The Cancer Genome Atlas (TCGA) database. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.2174/1389202919666181107122005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446481PMC
January 2019

Sequencing of human genomes with nanopore technology.

Nat Commun 2019 Apr 23;10(1):1869. Epub 2019 Apr 23.

Wellcome Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.

Whole-genome sequencing (WGS) is becoming widely used in clinical medicine in diagnostic contexts and to inform treatment choice. Here we evaluate the potential of the Oxford Nanopore Technologies (ONT) MinION long-read sequencer for routine WGS by sequencing the reference sample NA12878 and the genome of an individual with ataxia-pancytopenia syndrome and severe immune dysregulation. We develop and apply a novel reference panel-free analytical method to infer and then exploit phase information which improves single-nucleotide variant (SNV) calling performance from otherwise modest levels. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-019-09637-5DOI Listing

Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight.

Authors:
Leanne K Küpers Claire Monnereau Gemma C Sharp Paul Yousefi Lucas A Salas Akram Ghantous Christian M Page Sarah E Reese Allen J Wilcox Darina Czamara Anne P Starling Alexei Novoloaca Samantha Lent Ritu Roy Cathrine Hoyo Carrie V Breton Catherine Allard Allan C Just Kelly M Bakulski John W Holloway Todd M Everson Cheng-Jian Xu Rae-Chi Huang Diana A van der Plaat Matthias Wielscher Simon Kebede Merid Vilhelmina Ullemar Faisal I Rezwan Jari Lahti Jenny van Dongen Sabine A S Langie Tom G Richardson Maria C Magnus Ellen A Nohr Zongli Xu Liesbeth Duijts Shanshan Zhao Weiming Zhang Michelle Plusquin Dawn L DeMeo Olivia Solomon Joosje H Heimovaara Dereje D Jima Lu Gao Mariona Bustamante Patrice Perron Robert O Wright Irva Hertz-Picciotto Hongmei Zhang Margaret R Karagas Ulrike Gehring Carmen J Marsit Lawrence J Beilin Judith M Vonk Marjo-Riitta Jarvelin Anna Bergström Anne K Örtqvist Susan Ewart Pia M Villa Sophie E Moore Gonneke Willemsen Arnout R L Standaert Siri E Håberg Thorkild I A Sørensen Jack A Taylor Katri Räikkönen Ivana V Yang Katerina Kechris Tim S Nawrot Matt J Silver Yun Yun Gong Lorenzo Richiardi Manolis Kogevinas Augusto A Litonjua Brenda Eskenazi Karen Huen Hamdi Mbarek Rachel L Maguire Terence Dwyer Martine Vrijheid Luigi Bouchard Andrea A Baccarelli Lisa A Croen Wilfried Karmaus Denise Anderson Maaike de Vries Sylvain Sebert Juha Kere Robert Karlsson Syed Hasan Arshad Esa Hämäläinen Michael N Routledge Dorret I Boomsma Andrew P Feinberg Craig J Newschaffer Eva Govarts Matthieu Moisse M Daniele Fallin Erik Melén Andrew M Prentice Eero Kajantie Catarina Almqvist Emily Oken Dana Dabelea H Marike Boezen Phillip E Melton Rosalind J Wright Gerard H Koppelman Letizia Trevisi Marie-France Hivert Jordi Sunyer Monica C Munthe-Kaas Susan K Murphy Eva Corpeleijn Joseph Wiemels Nina Holland Zdenko Herceg Elisabeth B Binder George Davey Smith Vincent W V Jaddoe Rolv T Lie Wenche Nystad Stephanie J London Debbie A Lawlor Caroline L Relton Harold Snieder Janine F Felix

Nat Commun 2019 Apr 23;10(1):1893. Epub 2019 Apr 23.

The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (P < 1.06 x 10). Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-019-09671-3DOI Listing

Multiple myeloma immunoglobulin lambda translocations portend poor prognosis.

Nat Commun 2019 Apr 23;10(1):1911. Epub 2019 Apr 23.

Department of Hematology and Medical Oncology, Emory University School of Medicine, 1365 Clifton Rd. NE, Atlanta, GA, 30322, USA.

Multiple myeloma is a malignancy of antibody-secreting plasma cells. Most patients benefit from current therapies, however, 20% of patients relapse or die within two years and are deemed high risk. Here we analyze structural variants from 795 newly-diagnosed patients as part of the CoMMpass study. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-019-09555-6DOI Listing

A chemical toolbox for the study of bromodomains and epigenetic signaling.

Nat Commun 2019 Apr 23;10(1):1915. Epub 2019 Apr 23.

Structural Genomics Consortium, Buchmann Institute for Life Sciences, Goethe-University Frankfurt, 60438, Frankfurt, Germany.

Bromodomains (BRDs) are conserved protein interaction modules which recognize (read) acetyl-lysine modifications, however their role(s) in regulating cellular states and their potential as targets for the development of targeted treatment strategies is poorly understood. Here we present a set of 25 chemical probes, selective small molecule inhibitors, covering 29 human bromodomain targets. We comprehensively evaluate the selectivity of this probe-set using BROMOscan and demonstrate the utility of the set identifying roles of BRDs in cellular processes and potential translational applications. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-019-09672-2DOI Listing

PARP inhibitor efficacy depends on CD8+ T cell recruitment via intratumoral STING pathway activation in BRCA-deficient models of triple-negative breast cancer.

Cancer Discov 2019 Apr 23. Epub 2019 Apr 23.

Department of Medical Oncology, Dana-Farber Cancer Institute

Combinatorial clinical trials of PARP inhibitors with immunotherapies are ongoing, yet the immunomodulatory effects of PARP inhibition have been incompletely studied. Here, we sought to dissect the mechanisms underlying PARP inhibitor-induced changes in the tumor microenvironment of BRCA1-deficient triple-negative breast cancer (TNBC). We demonstrate that the PARP inhibitor olaparib induces CD8+ T cell infiltration and activation in vivo, and that CD8+ T cell depletion severely compromises anti-tumor efficacy. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1158/2159-8290.CD-18-1218DOI Listing
April 2019
2 Reads

Molecular Profiling of Tumor Tissue and Plasma Cell-Free DNA from Patients with Non-Langerhans Cell Histiocytosis.

Mol Cancer Ther 2019 Apr 23. Epub 2019 Apr 23.

Center for Personalized Cancer Therapy, Division of Blood and Marrow Transplantation, University of California San Diego Moores Cancer Center.

The BRAFV600E mutation and BRAF inhibitor responsiveness characterize ~50% of patients with the non-Langerhans cell histiocytosis (non-LCH) Erdheim-Chester disease (ECD). We interrogated the non-LCH molecular landscape (ECD, n=35; Rosai-Dorfman disease [RDD], n=3; mixed ECD/RDD, n=1) using BRAFV600E polymerase chain reaction and/or next-generation sequencing (tissue and cell-free DNA [cfDNA] of plasma and/or urine). Of 34 evaluable patients, 17 (50%) had the BRAFV600E mutation. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1158/1535-7163.MCT-18-1244DOI Listing

The Alternative Splicing Regulator Nova2 Constrains Vascular Erk Signaling to Limit Specification of the Lymphatic Lineage.

Dev Cell 2019 Apr;49(2):279-292.e5

Division of Genomics of Development and Disease, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, QLD 4073, Australia. Electronic address:

The correct assignment of cell fate within fields of multipotent progenitors is essential for accurate tissue diversification. The first lymphatic vessels arise from pre-existing veins after venous endothelial cells become specified as lymphatic progenitors. Prox1 specifies lymphatic fate and labels these progenitors; however, the mechanisms restricting Prox1 expression and limiting the progenitor pool remain unknown. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.devcel.2019.03.017DOI Listing

Interchromosomal template-switching as a novel molecular mechanism for imprinting perturbations associated with Temple syndrome.

Genome Med 2019 Apr 23;11(1):25. Epub 2019 Apr 23.

Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Room 604B, Houston, TX, 77030-3498, USA.

Background: Intrachromosomal triplications (TRP) can contribute to disease etiology via gene dosage effects, gene disruption, position effects, or fusion gene formation. Recently, post-zygotic de novo triplications adjacent to copy-number neutral genomic intervals with runs of homozygosity (ROH) have been shown to result in uniparental isodisomy (UPD). The genomic structure of these complex genomic rearrangements (CGRs) shows a consistent pattern of an inverted triplication flanked by duplications (DUP-TRP/INV-DUP) formed by an iterative DNA replisome template-switching mechanism during replicative repair of a single-ended, double-stranded DNA (seDNA), the ROH results from an interhomolog or nonsister chromatid template switch. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-019-0633-yDOI Listing

Combinations of immuno-checkpoint inhibitors predictive biomarkers only marginally improve their individual accuracy.

J Transl Med 2019 Apr 23;17(1):131. Epub 2019 Apr 23.

IRCCS Regina Elena National Cancer Institute, Rome, Italy.

Background: There are no accepted universal biomarkers capable to accurately predict response to immuno-checkpoint inhibitors (ICI). Although recent literature has been flooded with studies on ICI predictive biomarkers, available data show that currently approved companion diagnostics either leave out many possible responders, as in the case of PD-L1 testing for first-line metastatic lung cancer, or apply to a small subset of patients, such as the recently approved treatment for microsatellite instability-high or mismatch repair deficiency tumors. In this study, we conducted a survey of the available data on ICI trials with matched genomic or transcriptomic datasets in order to cross-validate the proposed biomarkers, to assess whether their prediction power was confirmed and, mainly, to investigate if their combination was able to generate a better predictive tool. Read More

View Article

Download full-text PDF

Source
https://translational-medicine.biomedcentral.com/articles/10
Publisher Site
http://dx.doi.org/10.1186/s12967-019-1865-8DOI Listing
April 2019
1 Read

Comprehensive kinome NGS targeted expression profiling by KING-REX.

BMC Genomics 2019 Apr 23;20(1):307. Epub 2019 Apr 23.

NMS Oncology, Nerviano Medical Sciences Srl, Nerviano, MI, Italy.

Background: Protein kinases are enzymes controlling different cellular functions. Genetic alterations often result in kinase dysregulation, making kinases a very attractive class of druggable targets in several human diseases. Existing approved drugs still target a very limited portion of the human 'kinome', demanding a broader functional knowledge of individual and co-expressed kinase patterns in physiologic and pathologic settings. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12864-019-5676-3DOI Listing

Computational Methods for Detection of Differentially Methylated Regions Using Kernel Distance and Scan Statistics.

Genes (Basel) 2019 Apr 12;10(4). Epub 2019 Apr 12.

Department of Population Health Sciences, Augusta University, Augusta, GA 30912, USA.

Motivation: Researchers in genomics are increasingly interested in epigenetic factors such as DNA methylation because they play an important role in regulating gene expression without changes in the sequence of DNA. Abnormal DNA methylation is associated with many human diseases.

Results: We propose two different approaches to test for differentially methylated regions (DMRs) associated with complex traits, while accounting for correlations among CpG sites in the DMRs. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.3390/genes10040298DOI Listing

Activating p53 family member TAp63: A novel therapeutic strategy for targeting p53-altered tumors.

Cancer 2019 Apr 23. Epub 2019 Apr 23.

Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia.

Background: Over 96% of high-grade ovarian carcinomas and 50% of all cancers are characterized by alterations in the p53 gene. Therapeutic strategies to restore and/or reactivate the p53 pathway have been challenging. By contrast, p63, which shares many of the downstream targets and functions of p53, is rarely mutated in cancer. Read More

View Article

Download full-text PDF

Source
https://onlinelibrary.wiley.com/doi/abs/10.1002/cncr.32053
Publisher Site
http://dx.doi.org/10.1002/cncr.32053DOI Listing
April 2019
1 Read

The Burden of Breast Cancer Predisposition Variants Across The Age Spectrum Among 10 000 Patients.

J Am Geriatr Soc 2019 Apr 23. Epub 2019 Apr 23.

Clinical Cancer Genomics, City of Hope Comprehensive Cancer Center, Duarte, California.

Background/objectives: Women diagnosed with breast cancer (BC) at an older age are less likely to undergo genetic cancer risk assessment and genetic testing since the guidelines and referrals are biased toward earlier age at diagnosis. Thus, we determined the prevalence and type of pathogenic cancer predisposition variants among women with a history of BC diagnosed at the age of 65 years or older vs younger than 65 years.

Design: Prospective registration cohort. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1111/jgs.15937DOI Listing

Spatial control of oxygen delivery to three-dimensional cultures alters cancer cell growth and gene expression.

J Cell Physiol 2019 Apr 22. Epub 2019 Apr 22.

Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Commonly used monolayer cancer cell cultures fail to provide a physiologically relevant environment in terms of oxygen delivery. Here, we describe a three-dimensional (3D) bioreactor system where cancer cells are grown in Matrigel in modified six-well plates. Oxygen is delivered to the cultures through a polydimethylsiloxane (PDMS) membrane at the bottom of the wells, with microfabricated PDMS pillars to control oxygen delivery. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcp.28665DOI Listing

Immunogenic neoantigens derived from gene fusions stimulate T cell responses.

Nat Med 2019 Apr 22. Epub 2019 Apr 22.

Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Anti-tumor immunity is driven by self versus non-self discrimination. Many immunotherapeutic approaches to cancer have taken advantage of tumor neoantigens derived from somatic mutations. Here, we demonstrate that gene fusions are a source of immunogenic neoantigens that can mediate responses to immunotherapy. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41591-019-0434-2DOI Listing

Multiplexed detection of proteins, transcriptomes, clonotypes and CRISPR perturbations in single cells.

Nat Methods 2019 Apr 22. Epub 2019 Apr 22.

Technology Innovation Laboratory, New York Genome Center, New York, NY, USA.

Multimodal single-cell assays provide high-resolution snapshots of complex cell populations, but are mostly limited to transcriptome plus an additional modality. Here, we describe expanded CRISPR-compatible cellular indexing of transcriptomes and epitopes by sequencing (ECCITE-seq) for the high-throughput characterization of at least five modalities of information from each single cell. We demonstrate application of ECCITE-seq to multimodal CRISPR screens with robust direct single-guide RNA capture and to clonotype-aware multimodal phenotyping of cancer samples. Read More

View Article

Download full-text PDF

Source
http://www.nature.com/articles/s41592-019-0392-0
Publisher Site
http://dx.doi.org/10.1038/s41592-019-0392-0DOI Listing
April 2019
3 Reads

Lineage-specific alterations in gynecologic neoplasms with choriocarcinomatous differentiation: implications for origin and therapeutics.

Clin Cancer Res 2019 Apr 22. Epub 2019 Apr 22.

Pathology, Johns Hopkins University.

Purpose: Choriocarcinoma is most commonly gestational (androgenetic or biparental) but can be of germ cell origin or can develop as a component of a somatic neoplasm (genetically related to the patient). The latter type are aggressive neoplasms for which the underlying genetic alterations are not well-characterized.

Experimental Design: To investigate the relationship between the different components of somatic neoplasms with choriocarcinomatous elements, the genetic differences between gestational and non-gestational tumors, and identify potential targetable alterations, we analyzed 23 samples from 11 tumors, including 5 gynecologic-type somatic neoplasms with choriocarcinomatous differentiation (2-3 different components each) and 6 pure choriocarcinomas, for somatic mutations, single nucleotide polymorphisms and PD-L1 expression. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-18-4278DOI Listing

Single-cell lymphocyte heterogeneity in advanced Cutaneous T-Cell Lymphoma skin tumors.

Clin Cancer Res 2019 Apr 22. Epub 2019 Apr 22.

Medicine, University of Pittsburgh School of Medicine

Purpose: The heterogeneity of tumor cells presents a major challenge to cancer diagnosis and therapy. Cutaneous T cell lymphomas (CTCL) are a group of T lymphocyte malignancies that primarily affect skin. Lack of highly specific markers for malignant lymphocytes prevents early diagnosis, while only limited treatment options are available for patients with advanced-stage CTCL. Read More

View Article

Download full-text PDF

Source
http://clincancerres.aacrjournals.org/lookup/doi/10.1158/107
Publisher Site
http://dx.doi.org/10.1158/1078-0432.CCR-19-0148DOI Listing
April 2019
3 Reads

Detection of Colorectal Cancer in Circulating Cell-Free DNA by Methylated CpG Tandem Amplification and Sequencing.

Clin Chem 2019 Apr 22. Epub 2019 Apr 22.

Beijing Advanced Innovation Center for Genomics, College of Life Sciences, Department of General Surgery, Third Hospital, Peking University, Beijing, China;

Background: Aberrant DNA hypermethylation of CpG islands occurs frequently throughout the genome in human colorectal cancer (CRC). A genome-wide DNA hypermethylation analysis technique using circulating cell-free DNA (cfDNA) is attractive for the noninvasive early detection of CRC and discrimination between CRC and other cancer types.

Methods: We applied the methylated CpG tandem amplification and sequencing (MCTA-Seq) method, with a fully methylated molecules algorithm, to plasma samples from patients with CRC (n = 147) and controls (n = 136), as well as cancer and adjacent noncancerous tissue samples (n = 66). Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1373/clinchem.2019.301804DOI Listing

Genomic Features, Comparative Genomic Analysis, and Antimicrobial Susceptibility Patterns of Strain ED882-96 Isolated in Taiwan.

Genes (Basel) 2019 Apr 20;10(4). Epub 2019 Apr 20.

School of Medicine, College of Medicine, I-Shou University, Kaohsiung 824, Taiwan.

Bacteria belonging to the genus are ubiquitously distributed in natural environments, plants, and animals. Except and , other species rarely cause human diseases. This study reported the whole-genome features, comparative genomic analysis, and antimicrobial susceptibility patterns of ED882-96 isolated in Taiwan. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.3390/genes10040309DOI Listing

Metabolic and epigenetic reprogramming in the arsenic-induced cancer stem cells.

Semin Cancer Biol 2019 Apr 19. Epub 2019 Apr 19.

Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI, 48201, USA. Electronic address:

At present, the belief that genetic mutations control every aspect of tumorigenesis is still very popular. Even for the highly debated "bad luck" theory of cancers, it ascertained that random mutation of genes during the self-renewal of somatic stem cells is responsible for cancer initiation. Logically, most of the new therapeutic strategies so far, from molecular targeting to precision medicine or personalized medicine, are genome-obsessed and focused on identifying and targeting these mutated genes. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.semcancer.2019.04.003DOI Listing

Chemotherapy-induced peripheral neuropathy: where are we now?

Authors:
Lesley A Colvin

Pain 2019 May;160 Suppl 1:S1-S10

Chair of Pain Medicine, Division of Population Health and Genomics, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major challenge, with increasing impact as oncological treatments, using potentially neurotoxic chemotherapy, improve cancer cure and survival. Acute CIPN occurs during chemotherapy, sometimes requiring dose reduction or cessation, impacting on survival. Around 30% of patients will still have CIPN a year, or more, after finishing chemotherapy. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1097/j.pain.0000000000001540DOI Listing

A comprehensive reference transcriptome resource for the Iberian ribbed newt Pleurodeles waltl, an emerging model for developmental and regeneration biology.

DNA Res 2019 Apr 22. Epub 2019 Apr 22.

Department of Biomedical Sciences, School of Life Science, Faculty of Medicine, Tottori University, Yonago, Tottori 683-8503, Japan.

Urodele newts have unique biological properties, notably including prominent regeneration ability. The Iberian ribbed newt, Pleurodeles waltl, is a promising model amphibian distinguished by ease of breeding and efficient transgenic and genome editing methods. However, limited genetic information is available for P. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1093/dnares/dsz003DOI Listing

Defective DNA Polymerase α-Primase Leads to X-Linked Intellectual Disability Associated with Severe Growth Retardation, Microcephaly, and Hypogonadism.

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

Genome Damage and Stability Centre, University of Sussex, BN1 9RQ Sussex, UK. Electronic address:

Replicating the human genome efficiently and accurately is a daunting challenge involving the duplication of upward of three billion base pairs. At the core of the complex machinery that achieves this task are three members of the B family of DNA polymerases: DNA polymerases α, δ, and ε. Collectively these multimeric polymerases ensure DNA replication proceeds at optimal rates approaching 2 × 10 nucleotides/min with an error rate of less than one per million nucleotides polymerized. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajhg.2019.03.006DOI Listing

A PET study in healthy subjects of brain exposure of C-labelled osimertinib - A drug intended for treatment of brain metastases in non-small cell lung cancer.

J Cereb Blood Flow Metab 2019 Apr 20:271678X19843776. Epub 2019 Apr 20.

1 Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet and Stockholm County Council, Stockholm, Sweden.

Osimertinib is a tyrosine kinase inhibitor (TKI) of the mutated epidermal growth factor receptor (EGFRm) with observed efficacy in patients with brain metastases. Brain exposure and drug distribution in tumor regions are important criteria for evaluation and confirmation of CNS efficacy. The aim of this PET study was therefore to determine brain distribution and exposure of C-labelled osimertinib administered intravenously in subjects with an intact blood-brain barrier. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1177/0271678X19843776DOI Listing
April 2019
1 Read

Cervical cancer genomics: an initial step towards personalized approach to therapy.

EBioMedicine 2019 Apr 17. Epub 2019 Apr 17.

Molecular Pathology Laboratory, Department of Cytology and Gynecological Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India. Electronic address:

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2019.04.025DOI Listing

An international, phase III randomized trial in patients with mucinous epithelial ovarian cancer (mEOC/GOG 0241) with long-term follow-up: and experience of conducting a clinical trial in a rare gynecological tumor.

Gynecol Oncol 2019 Apr 17. Epub 2019 Apr 17.

The University of Texas MD Anderson Cancer Centre, Houston, TX, USA.

Objectives: We evaluated four different treatment regimens for advanced-stage mucinous epithelial ovarian cancer.

Methods: We conducted a multicenter randomized factorial trial (UK and US). Patients were diagnosed with primary mEOC: FIGO stage II-IV or recurrence after stage I disease. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygyno.2019.03.256DOI Listing

P300 Acetyltransferase is a Cytoplasm-to-Nucleus Shuttle for SMAD2/3 and TAZ Nuclear Transport in TGFβ-stimulated Hepatic Stellate Cells.

Hepatology 2019 Apr 20. Epub 2019 Apr 20.

Tumor Microenvironment and Metastasis, Hormel Institute, University of Minnesota, Austin, MN, USA.

Nuclear translocation of SMAD2/3, core transcription factors of TGFβ signaling, is critical for hepatic stellate cell (HSC) differentiation into metastasis-promoting myofibroblasts. SMAD2/3 have multiple coactivators, including WW domain-containing transcription regulator protein 1 (WWTR1 or TAZ) and p300 acetyltransferase. In the nucleus, TAZ binds to SMAD2/3 to prevent SMAD2/3 nuclear export. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.30668DOI Listing

A novel de novo PDGFRB variant in a child with severe cerebral malformations, intracerebral calcifications, and infantile myofibromatosis.

Am J Med Genet A 2019 Apr 19. Epub 2019 Apr 19.

Laboratory of embryology and genetics of malformations, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1163, Institut Imagine, Paris, France.

The spectrum of clinical consequences of variants in the Platelet derived growth factor receptor beta (PDGFRB) gene is wide. Missense variants leading to variable loss of signal transduction in vitro have been reported in the idiopathic basal ganglia calcification (IBGC) syndrome Type 4. In contrast, gain-of-function variants have been reported in infantile myofibromatosis, Penttinen syndrome, and Kosaki overgrowth syndrome. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.a.61151DOI Listing

In silico markers: an evolutionary and statistical approach to select informative genes of human breast cancer subtypes.

Genes Genomics 2019 Apr 19. Epub 2019 Apr 19.

Department of Informatics, University of Evora, 7004-516, Evora, Portugal.

Background: Recent advancement in bioinformatics offers the ability to identify informative genes from high dimensional gene expression data. Selection of informative genes from these large datasets has emerged as an issue of major concern among researchers.

Objective: Gene functionality and regulatory mechanisms can be understood through the analysis of these gene expression data. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13258-019-00816-8DOI Listing
April 2019
1 Read

Clonal haematopoiesis and risk of acute myeloid leukemia.

Haematologica 2019 Apr 19. Epub 2019 Apr 19.

Washington University School of Medicine;

Nearly all adults harbor acute myeloid leukemia-related clonal hematopoietic mutations at a variant allele fraction of ≥0.0001, yet relatively few develop hematologic malignancies. We conducted a nested analysis in the Nurses' Health Study and Health Professionals Follow-Up Study blood subcohorts, with up to 22 years of follow-up, to investigate associations of clonal mutations of ≥0. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.3324/haematol.2018.215269DOI Listing
April 2019
2 Reads

Phenotypic and Genomic Determinants of Immunotherapy Response Associated with Squamousness.

Cancer Immunol Res 2019 Apr 19. Epub 2019 Apr 19.

Center for Personalized Cancer Therapy, Division of Blood and Marrow Transplantation, University of California San Diego Moores Cancer Center.

Advanced and metastatic squamous cell carcinomas (SCCs) are common and difficult-to-treat malignancies. We assessed 75 immunotherapy-treated SCC patients from a clinically annotated database of 2,651 patients, as well as 9,407 patients from a de-identified database for molecular features that might influence checkpoint blockade response. SCCs had higher tumor mutational burdens (TMB) than non-SCCs (P <0. Read More

View Article

Download full-text PDF

Source
http://cancerimmunolres.aacrjournals.org/lookup/doi/10.1158/
Publisher Site
http://dx.doi.org/10.1158/2326-6066.CIR-18-0716DOI Listing
April 2019
2 Reads

Genome-wide Burden of Rare Short Deletions Is Enriched in Major Depressive Disorder in Four Cohorts.

Biol Psychiatry 2019 Mar 13. Epub 2019 Mar 13.

Department of Genetics, Stanford University School of Medicine, Stanford, California. Electronic address:

Background: Major depressive disorder (MDD) is moderately heritable, with a high prevalence and a presumed high heterogeneity. Copy number variants (CNVs) could contribute to the heritable component of risk, but the two previous genome-wide association studies of rare CNVs did not report significant findings.

Methods: In this meta-analysis of four cohorts (5780 patients and 6626 control subjects), we analyzed the association of MDD to 1) genome-wide burden of rare deletions and duplications, partitioned by length (<100 kb or >100 kb) and other characteristics, and 2) individual rare exonic CNVs and CNV regions. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopsych.2019.02.022DOI Listing
March 2019
3 Reads

Altered Expression and Localization of Tumor Suppressive E3 Ubiquitin Ligase SMURF2 in Human Prostate and Breast Cancer.

Cancers (Basel) 2019 Apr 18;11(4). Epub 2019 Apr 18.

Laboratory of Molecular and Cellular Cancer Biology, Azrieli Faculty of Medicine, Bar-Ilan University, 1311502 Safed, Israel.

SMURF2, an E3 ubiquitin ligase and suggested tumor suppressor, operates in normal cells to prevent genomic instability and carcinogenesis. However, the mechanisms underlying SMURF2 inactivation in human malignancies remain elusive, as is rarely found mutated or deleted in cancers. We hypothesized that SMURF2 might have a distinct molecular biodistribution in cancer versus normal cells and tissues. Read More

View Article

Download full-text PDF

Source
https://www.mdpi.com/2072-6694/11/4/556
Publisher Site
http://dx.doi.org/10.3390/cancers11040556DOI Listing
April 2019
1 Read

miR‑145‑5p is associated with pathological complete response to neoadjuvant chemotherapy and impairs cell proliferation by targeting TGFβR2 in breast cancer.

Oncol Rep 2019 Jun 5;41(6):3527-3534. Epub 2019 Apr 5.

Genomics Sciences Program, Autonomous University of Mexico City, Mexico City 03100, Mexico.

Cancer patients who better benefit from neoadjuvant chemotherapy (NeoCh) are those who achieve a successful pathological complete response (pCR) represented by the absence of residual disease. Unfortunately, no highly sensitive and specific tumor biomarkers for predicting the clinical response to NeoCh have yet been defined. The aim of the present study was to ascertain whether miR‑145‑5p could discriminate between pCR and no‑pCR in triple‑negative breast cancer patients that received a cisplatin/doxorubicin‑based neoadjuvant treatment. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.3892/or.2019.7102DOI Listing

Evaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American Women.

Cancer Med 2019 Apr 18. Epub 2019 Apr 18.

Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia.

An association between genetic variants in the vitamin D receptor (VDR) gene and epithelial ovarian cancer (EOC) was previously reported in women of African ancestry (AA). We sought to examine associations between genetic variants in VDR and additional genes from vitamin D biosynthesis and pathway targets (EGFR, UGT1A, UGT2A1/2, UGT2B, CYP3A4/5, CYP2R1, CYP27B1, CYP24A1, CYP11A1, and GC). Genotyping was performed using the custom-designed 533,631 SNP Illumina OncoArray with imputation to the 1,000 Genomes Phase 3 v5 reference set in 755 EOC cases, including 537 high-grade serous (HGSOC), and 1,235 controls. Read More

View Article

Download full-text PDF

Source
https://onlinelibrary.wiley.com/doi/abs/10.1002/cam4.1996
Publisher Site
http://dx.doi.org/10.1002/cam4.1996DOI Listing
April 2019
2 Reads

miR-197-5p inhibits sarcomagenesis and induces cellular senescence via repression of KIAA0101.

Mol Carcinog 2019 Apr 18. Epub 2019 Apr 18.

RNAi and Functional Genomics Lab, Department of Life Science, National Institute of Technology, Rourkela, Odisha, India.

The abnormal expressions of microRNAs (miRNAs) are known to be associated with various pathophysiological processes that lead to the development of a plethora of diseases including cancer. Among several miRNAs studied so far, miR-197 has been reported to play a vital role either as an oncogene or tumor suppressor in different cancers. However, its role in carcinogenesis of fibrosarcoma has not yet been elucidated. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/mc.23021DOI Listing

Random gene sets in predicting survival of patients with hepatocellular carcinoma.

J Mol Med (Berl) 2019 Apr 17. Epub 2019 Apr 17.

Division of Hepatology & Division of Clinical Bioinformatics, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.

Despite multiple publications, molecular signatures predicting the course of hepatocellular carcinoma (HCC) have not yet been integrated into clinical routine decision-making. Given the diversity of published signatures, optimal number, best combinations, and benefit of functional associations of genes in prognostic signatures remain to be defined. We investigated a vast number of randomly chosen gene sets (varying between 1 and 10,000 genes) to encompass the full range of prognostic gene sets on 242 transcriptomic profiles of patients with HCC. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00109-019-01764-2DOI Listing
April 2019
2 Reads

Regulation of estrogen signaling and breast cancer proliferation by an ubiquitin ligase TRIM56.

Oncogenesis 2019 Apr 18;8(5):30. Epub 2019 Apr 18.

Henan Key Laboratory of Immunology and Targeted Therapy, School of Laboratory Medicine, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, 453003, Xinxiang, Henan, P.R. China.

Breast cancer ranks no. 1 in women cancer worldwide, while 60-70% are estrogen receptor alpha positive. The estrogen selective modulators, such as tamoxifen, become the effective drugs for controlling ER alpha breast cancer progression. Read More

View Article

Download full-text PDF

Source
http://www.nature.com/articles/s41389-019-0139-x
Publisher Site
http://dx.doi.org/10.1038/s41389-019-0139-xDOI Listing
April 2019
1 Read

Cystine/glutamate antiporter xCT (SLC7A11) facilitates oncogenic RAS transformation by preserving intracellular redox balance.

Proc Natl Acad Sci U S A 2019 Apr 18. Epub 2019 Apr 18.

Department of Molecular Oncology, BC Cancer, Vancouver V5Z 1L3, Canada;

The family of proto-oncogenes are among the most commonly mutated genes in human cancers and predict poor clinical outcome. Several mechanisms underlying oncogenic RAS transformation are well documented, including constitutive signaling through the RAF-MEK-ERK proproliferative pathway as well as the PI3K-AKT prosurvival pathway. Notably, control of redox balance has also been proposed to contribute to RAS transformation. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1821323116DOI Listing
April 2019
1 Read

MDM4 is targeted by 1q gain and drives disease in Burkitt lymphoma.

Cancer Res 2019 Apr 18. Epub 2019 Apr 18.

University Hospital and University of Zurich

Oncogenic MYC activation promotes proliferation in Burkitt lymphoma (BL), but also induces cell cycle arrest and apoptosis mediated by p53, a tumor suppressor that is mutated in 40% of BL cases. To identify molecular dependencies in BL, we performed RNAi-based, loss-of-function screening in eight BL cell lines and integrated non-BL RNAi screens and genetic data. We identified 76 genes essential to BL, including genes associated with hematopoietic cell differentiation (FLI1, BCL11A) or B cell development and activation (PAX5, CDKN1B, JAK2, CARD11) and found a number of context-specific dependencies including oncogene addiction in cell lines with TCF3/ID3 or MYD88 mutation. Read More

View Article

Download full-text PDF

Source
http://cancerres.aacrjournals.org/lookup/doi/10.1158/0008-54
Publisher Site
http://dx.doi.org/10.1158/0008-5472.CAN-18-3438DOI Listing
April 2019
2 Reads