49,884 results match your criteria Cancer genomics & proteomics[Journal]


Expansion of the phenotypic spectrum of de novo missense variants in kinesin family member 1A (KIF1A).

Hum Mutat 2020 Jul 11. Epub 2020 Jul 11.

Brain and Mitochondrial Research Group, Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia.

Defects in the motor domain of kinesin family member 1A (KIF1A), a neuron-specific ATP-dependent anterograde axonal transporter of synaptic cargo, are well-recognized to cause a spectrum of neurological conditions, commonly known as KIF1A-associated neurological disorders (KAND). Here we report one mutation-negative female with classic Rett syndrome (RTT) harboring a de novo heterozygous novel variant [NP_001230937.1:p. Read More

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http://dx.doi.org/10.1002/humu.24079DOI Listing

Osimertinib improves overall survival in EGFR-mutated non-small cell lung cancer patients with leptomeningeal metastases regardless of T790M mutational status.

J Thorac Oncol 2020 Jul 8. Epub 2020 Jul 8.

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. Electronic address:

Introduction: Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), efficiently penetrates the blood-brain barrier. Current study explored whether treatment with osimertinib leads to improved overall survival (OS) for EGFR-mutated NSCLC patients with leptomeningeal metastases (LM) compared with those not treated with osimertinib.

Methods: From October 2008 to October 2019, patients with EGFR-mutated NSCLC and cytologically confirmed LM were retrospectively analyzed for OS according to osimertinib treatment and T790M mutational status. Read More

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http://dx.doi.org/10.1016/j.jtho.2020.06.018DOI Listing

Bromodomain-selective BET inhibitors are potent antitumor agents against MYC-driven pediatric cancer.

Cancer Res 2020 Jul 10. Epub 2020 Jul 10.

Chemical Biology and Therapeutics, St. Jude Children's Research Hospital

Inhibition of members of the bromodomain and extra terminal (BET) family of proteins has proven a valid strategy for cancer chemotherapy. All BET identified to date contain two bromodomains (BD; BD1 and BD2) that are necessary for recognition of acetylated lysine residues in the N-terminal regions of histones. Chemical matter that targets BET (BETi) also interact via these domains. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-19-3934DOI Listing
July 2020
9.329 Impact Factor

The immunogenetic diversity of the HLA system in Mexico correlates with underlying population genetic structure.

Authors:
Rodrigo Barquera Diana Iraíz Hernández-Zaragoza Alicia Bravo-Acevedo Esteban Arrieta-Bolaños Stephen Clayton Víctor Acuña-Alonzo Julio César Martínez-Álvarez Concepción López-Gil Carmen Adalid-Sáinz María Del Rosario Vega-Martínez Araceli Escobedo-Ruíz Eva Dolores Juárez-Cortés Alexander Immel Hanna Pacheco-Ubaldo Liliana González-Medina Abraham Lona-Sánchez Julio Lara-Riegos María Guadalupe de Jesús Sánchez-Fernández Rosario Díaz-López Gregorio Ulises Guizar-López Carolina Elizabeth Medina-Escobedo María Araceli Arrazola-García Gustavo Daniel Montiel-Hernández Ofelia Hernández-Hernández Flor Del Rocío Ramos-de la Cruz Francisco Juárez-Nicolás Jorge Arturo Pantoja-Torres Tirzo Jesús Rodríguez-Munguía Vicencio Juárez-Barreto Héctor Delgado-Aguirre Ariadna Berenice Escutia-González Isis Goné-Vázquez Gamaliel Benítez-Arvizu Francia Paulina Arellano-Prado Víctor Eduardo García-Arias Marla Estefanía Rodríguez-López Patricia Méndez-Mani Raquel García-Álvarez Marisela Del Rocío González-Martínez Guadalupe Aquino-Rubio Néstor Escareño-Montiel Tannya Verónica Vázquez-Castillo María Guadalupe Uribe-Duarte María de Jesús Ruíz-Corral Andrea Ortega-Yáñez Natalia Bernal-Felipe Benjamín Gómez-Navarro Agustín Jericó Arriaga-Perea Virginia Martínez-Bezies Rosa María Macías-Medrano Jesús Abraham Aguilar-Campos Raúl Solís-Martínez Ricardo Serrano-Osuna Mario J Sandoval-Sandoval Yolanda Jaramillo-Rodríguez Antonio Salgado-Adame Federico Juárez-de la Cruz Bárbara Novelo-Garza María de Los Ángeles Pavón-Vargas Norma Salgado-Galicia Maria Cátira Bortolini Carla Gallo Gabriel Bedoya Francisco Rothhammer Rolando González-José Andrés Ruiz-Linares Samuel Canizales-Quinteros Sandra Romero-Hidalgo Johannes Krause Joaquín Zúñiga Edmond J Yunis Carolina Bekker-Méndez Julio Granados

Hum Immunol 2020 Jul 7. Epub 2020 Jul 7.

Department of Transplantation, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" (INCMNSZ), Mexico City, Mexico. Electronic address:

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) allele groups and alleles by PCR-SSP based typing in a total of 15,318 mixed ancestry Mexicans from all the states of the country divided into 78 sample sets, providing information regarding allelic and haplotypic frequencies and their linkage disequilibrium, as well as admixture estimates and genetic substructure. We identified the presence of 4268 unique HLA extended haplotypes across Mexico and find that the ten most frequent (HF > 1%) HLA haplotypes with significant linkage disequilibrium (Δ'≥0.1) in Mexico (accounting for 20% of the haplotypic diversity of the country) are of primarily Native American ancestry (A*02~B*39~DRB1*04~DQB1*03:02, A*02~B*35~DRB1*08~DQB1*04, A*68~B*39~DRB1*04~DQB1*03:02, A*02~B*35~DRB1*04~DQB1*03:02, A*24~B*39~DRB1*14~DQB1*03:01, A*24~B*35~DRB1*04~DQB1*03:02, A*24~B*39~DRB1*04~DQB1*03:02, A*02~B*40:02~DRB1*04~DQB1*03:02, A*68~B*35~DRB1*04~DQB1*03:02, A*02~B*15:01~DRB1*04~DQB1*03:02). Read More

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http://dx.doi.org/10.1016/j.humimm.2020.06.008DOI Listing

lncRNA HOTAIR overexpression induced downregulation of c-Met signaling promotes hybrid epithelial/mesenchymal phenotype in hepatocellular carcinoma cells.

Cell Commun Signal 2020 Jul 11;18(1):110. Epub 2020 Jul 11.

Izmir Biomedicine and Genome Center (IBG), Balcova, 35340, Izmir, Turkey.

Background: Epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) are both reversible processes, and regulation of phenotypical transition is very important for progression of several cancers including hepatocellular carcinoma (HCC). Recently, it is defined that cancer cells can attain a hybrid epithelial/mesenchymal (hybrid E/M) phenotype. Cells with hybrid E/M phenotype comprise mixed epithelial and mesenchymal properties, they can be more resistant to therapeutics and also more capable of initiating metastatic lesions. Read More

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http://dx.doi.org/10.1186/s12964-020-00602-0DOI Listing

Quantitative characterization of tumor cell-free DNA shortening.

BMC Genomics 2020 Jul 10;21(1):473. Epub 2020 Jul 10.

Department of Oncology, Xiangya Hospital, Central South University, 87 Xiangya Rd, Changsha, 410008, Hunan Province, China.

Background: Previous studies found that cell-free DNA (cfDNA) generated from tumors was shorter than that from healthy cells, and selecting short cfDNA could enrich for tumor cfDNA and improve its usage in early cancer diagnosis and treatment monitoring; however, the underlying mechanism of shortened tumor cfDNA was still unknown, which potentially limits its further clinical application.

Results: Using targeted sequencing of cfDNA in a large cohort of solid tumor patient, sequencing reads harboring tumor-specific somatic mutations were isolated to examine the exact size distribution of tumor cfDNA. For the majority of studied cases, 166 bp remained as the peak size of tumor cfDNA, with tumor cfDNA showing an increased proportion of short fragments (100-150 bp). Read More

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http://dx.doi.org/10.1186/s12864-020-06848-9DOI Listing

Antithymocyte Globulin for Matched Sibling Donor Transplantation in Patients With Hematologic Malignancies: A Multicenter, Open-Label, Randomized Controlled Study.

J Clin Oncol 2020 Jul 10:JCO2000150. Epub 2020 Jul 10.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, and Peking-Tsinghua Center for Life Sciences, Beijing, China.

Purpose: The role of antithymocyte globulin (ATG) in preventing acute graft-versus-host disease (aGVHD) after HLA-matched sibling donor transplantation (MSDT) is still controversial.

Patients And Methods: We performed a prospective, multicenter, open-label, randomized controlled trial (RCT) across 23 transplantation centers in China. Patients ages 40-60 years with standard-risk hematologic malignancies with an HLA-matched sibling donor were randomly assigned to an ATG group (4. Read More

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http://dx.doi.org/10.1200/JCO.20.00150DOI Listing

Presenting Features and Early Mortality from SARS-CoV-2 Infection in Cancer Patients during the Initial Stage of the COVID-19 Pandemic in Europe.

Cancers (Basel) 2020 Jul 8;12(7). Epub 2020 Jul 8.

Department of Translational Medicine, Division of Oncology, University of Piemonte Orientale and Maggiore della Carita' Hospital, 28100 Novara, Italy.

We describe the outcomes in cancer patients during the initial outbreak of the COVID-19 in Europe from the retrospective, multi-center observational OnCovid study. We identified 204 cancer patients from eight centers in the United Kingdom, Italy, and Spain aged > 18 (mean = 69) and diagnosed with COVID-19 between February 26th and April 1st, 2020. A total of 127 (62%) were male, 184 (91%) had a diagnosis of solid malignancy, and 103 (51%) had non-metastatic disease. Read More

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http://dx.doi.org/10.3390/cancers12071841DOI Listing

Parsing the functional specificity of Siderocalin/Lipocalin 2/NGAL for siderophores and related small-molecule ligands.

J Struct Biol X 2019 Apr-Jun;2:100008. Epub 2019 May 30.

Division of Basic Science, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

Siderocalin/Lipocalin 2/Neutrophil Gelatinase Associated Lipocalin/24p3 is an innate immune system protein with bacteriostatic activity, acting by tightly binding and sequestering diverse catecholate and mixed-type ferric siderophores from enteric bacteria and mycobacteria. Bacterial virulence achieved through siderophore modifications, or utilization of alternate siderophores, can be explained by evasion of Siderocalin binding. Siderocalin has also been implicated in a wide variety of disease processes, though often in seemingly contradictory ways, and has been proposed to bind to a broader array of ligands beyond siderophores. Read More

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http://dx.doi.org/10.1016/j.yjsbx.2019.100008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337064PMC

Association of LINC00673 rs11655237 polymorphism with cancer susceptibility: A meta-analysis based on 23,478 subjects.

Genomics 2020 Jul 7. Epub 2020 Jul 7.

Department of Epidemiology, School of Public Health, China Medical University, Shenyang 110122, PR China; Key Laboratory of Cancer Etiology and Intervention, University of Liaoning Province, Shenyang 110122, PR China. Electronic address:

Background: Some studies on the relationship between LINC00673 polymorphism and cancer susceptibility have been inconsistent. To perform a more comprehensively quantitative assessment of LINC00673 rs11655237 and risk of overall cancer, we operated this meta-analysis for the first time.

Methods: A comprehensive search was conducted to obtain relevant literature up to November 20, 2019. Read More

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http://dx.doi.org/10.1016/j.ygeno.2020.07.015DOI Listing

Immunogenomic Landscape of Hematological Malignancies.

Cancer Cell 2020 Jun 24. Epub 2020 Jun 24.

Hematology Research Unit Helsinki, Helsinki University Hospital Comprehensive Cancer Center (HUH CCC), 00029 Helsinki, Finland; Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki (UH), 00029 Helsinki, Finland; iCAN Digital Precision Cancer Medicine Flagship, Helsinki, Finland. Electronic address:

Understanding factors that shape the immune landscape across hematological malignancies is essential for immunotherapy development. We integrated over 8,000 transcriptomes and 2,000 samples with multilevel genomics of hematological cancers to investigate how immunological features are linked to cancer subtypes, genetic and epigenetic alterations, and patient survival, and validated key findings experimentally. Infiltration of cytotoxic lymphocytes was associated with TP53 and myelodysplasia-related changes in acute myeloid leukemia, and activated B cell-like phenotype and interferon-γ response in lymphoma. Read More

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http://dx.doi.org/10.1016/j.ccell.2020.06.002DOI Listing

Across the Globe: Proteogenomic Landscapes of Lung Cancer.

Cell 2020 Jul;182(1):9-11

Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address:

In this issue of Cell, articles by Gillette et al., Chen et al., and Xu, et al. Read More

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http://dx.doi.org/10.1016/j.cell.2020.06.016DOI Listing

Integrative Proteomic Characterization of Human Lung Adenocarcinoma.

Cell 2020 Jul;182(1):245-261.e17

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of the Chinese Academy of Sciences, Beijing, China. Electronic address:

Genomic studies of lung adenocarcinoma (LUAD) have advanced our understanding of the disease's biology and accelerated targeted therapy. However, the proteomic characteristics of LUAD remain poorly understood. We carried out a comprehensive proteomics analysis of 103 cases of LUAD in Chinese patients. Read More

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http://dx.doi.org/10.1016/j.cell.2020.05.043DOI Listing

Proteogenomics of Non-smoking Lung Cancer in East Asia Delineates Molecular Signatures of Pathogenesis and Progression.

Cell 2020 Jul;182(1):226-244.e17

Institute of Chemistry, Academia Sinica, Taipei, Taiwan; Department of Chemistry, National Taiwan University, Taipei, Taiwan. Electronic address:

Lung cancer in East Asia is characterized by a high percentage of never-smokers, early onset and predominant EGFR mutations. To illuminate the molecular phenotype of this demographically distinct disease, we performed a deep comprehensive proteogenomic study on a prospectively collected cohort in Taiwan, representing early stage, predominantly female, non-smoking lung adenocarcinoma. Integrated genomic, proteomic, and phosphoproteomic analysis delineated the demographically distinct molecular attributes and hallmarks of tumor progression. Read More

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http://dx.doi.org/10.1016/j.cell.2020.06.012DOI Listing

Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma.

Cell 2020 Jul;182(1):200-225.e35

Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA. Electronic address:

To explore the biology of lung adenocarcinoma (LUAD) and identify new therapeutic opportunities, we performed comprehensive proteogenomic characterization of 110 tumors and 101 matched normal adjacent tissues (NATs) incorporating genomics, epigenomics, deep-scale proteomics, phosphoproteomics, and acetylproteomics. Multi-omics clustering revealed four subgroups defined by key driver mutations, country, and gender. Proteomic and phosphoproteomic data illuminated biology downstream of copy number aberrations, somatic mutations, and fusions and identified therapeutic vulnerabilities associated with driver events involving KRAS, EGFR, and ALK. Read More

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http://dx.doi.org/10.1016/j.cell.2020.06.013DOI Listing

A Genetic Map of the Response to DNA Damage in Human Cells.

Cell 2020 Jul 9. Epub 2020 Jul 9.

Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. Electronic address:

The response to DNA damage is critical for cellular homeostasis, tumor suppression, immunity, and gametogenesis. In order to provide an unbiased and global view of the DNA damage response in human cells, we undertook 31 CRISPR-Cas9 screens against 27 genotoxic agents in the retinal pigment epithelium-1 (RPE1) cell line. These screens identified 890 genes whose loss causes either sensitivity or resistance to DNA-damaging agents. Read More

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http://dx.doi.org/10.1016/j.cell.2020.05.040DOI Listing

A Platelet Function Modulator of Thrombin Activation Is Causally Linked to Cardiovascular Disease and Affects PAR4 Receptor Signaling.

Am J Hum Genet 2020 Jul 4. Epub 2020 Jul 4.

National Heart, Lung, and Blood Institute, Division of Intramural Research, Population Sciences Branch, The Framingham Heart Study, Framingham, MA 01702, USA. Electronic address:

Dual antiplatelet therapy reduces ischemic events in cardiovascular disease, but it increases bleeding risk. Thrombin receptors PAR1 and PAR4 are drug targets, but the role of thrombin in platelet aggregation remains largely unexplored in large populations. We performed a genome-wide association study (GWAS) of platelet aggregation in response to full-length thrombin, followed by clinical association analyses, Mendelian randomization, and functional characterization including iPSC-derived megakaryocyte and platelet experiments. Read More

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http://dx.doi.org/10.1016/j.ajhg.2020.06.008DOI Listing

The novel reversible LSD1 inhibitor SP-2577 promotes anti-tumor immunity in SWItch/Sucrose-NonFermentable (SWI/SNF) complex mutated ovarian cancer.

PLoS One 2020 10;15(7):e0235705. Epub 2020 Jul 10.

Applied Cancer Research and Drug Discovery Division, Translational Genomics Research Institute (TGen) of City of Hope, Phoenix, Arizona, United States of America.

Mutations of the SWI/SNF chromatin remodeling complex occur in 20% of all human cancers, including ovarian cancer. Approximately half of ovarian clear cell carcinomas (OCCC) carry mutations in the SWI/SNF subunit ARID1A, while small cell carcinoma of the ovary hypercalcemic type (SCCOHT) presents with inactivating mutations of the SWI/SNF ATPase SMARCA4 alongside epigenetic silencing of the ATPase SMARCA2. Loss of these ATPases disrupts SWI/SNF chromatin remodeling activity and may also interfere with the function of other histone-modifying enzymes that associate with or are dependent on SWI/SNF activity. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235705PLOS

Single-nucleotide polymorphism biomarkers of adjuvant anastrozole-induced estrogen suppression in early breast cancer.

Pharmacogenet Genomics 2020 Jul 8. Epub 2020 Jul 8.

Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.

Objective: Based on our previous findings that postmenopausal women with estrone (E1) and estradiol (E2) concentrations at or above 1.3 pg/ml and 0.5 pg/ml, respectively, after 6 months of adjuvant anastrozole therapy had a three-fold risk of recurrence, we aimed to identify a single-nucleotide polymorphism (SNP)-based model that would predict elevated E1 and E2 and then validate it in an independent dataset. Read More

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http://dx.doi.org/10.1097/FPC.0000000000000415DOI Listing

Equity in Genomics: A Brief Report on Cardiovascular Health Disparities in African American Adults.

J Cardiovasc Nurs 2020 Jul 1. Epub 2020 Jul 1.

Jewel Scott, PhD, MSN, FNP-C Doctoral Trainee, Duke University School of Nursing, Durham, North Carolina. Lakeshia Cousin, PhD, APRN Postdoctoral Fellow, Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, Florida. Jennifer Woo, PhD, CNM/WHNP, FACNM Assistant Professor, Texas Women's University, Dallas. Rosa Gonzalez-Guarda, PhD, MPH, RN, CPH, FAAN Associate Professor, Duke University School of Nursing, Durham, North Carolina. Leigh Ann Simmons, PhD, MFT Professor and Chair, Department of Human Ecology, University of California, Davis.

Background: African Americans are more likely to die from cardiovascular disease (CVD) than all other populations in the United States. Although technological advances have supported rapid growth in applying genetics/genomics to address CVD, most research has been conducted among European Americans. The lack of African American representation in genomic samples has limited progress in equitably applying precision medicine tools, which will widen CVD disparities if not remedied. Read More

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http://dx.doi.org/10.1097/JCN.0000000000000725DOI Listing

A transcriptomic study for identifying cardia- and non-cardia-specific gastric cancer prognostic factors using genetic algorithm-based methods.

J Cell Mol Med 2020 Jul 10. Epub 2020 Jul 10.

Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.

Gastric cancer (GC) is a heterogeneous tumour with numerous differences of epidemiologic and clinicopathologic features between cardia cancer and non-cardia cancer. However, few studies were performed to construct site-specific GC prognostic models. In this study, we identified site-specific GC transcriptomic prognostic biomarkers using genetic algorithm (GA)-based support vector machine (GA-SVM) and GA-based Cox regression method (GA-Cox) in the Cancer Genome Atlas (TCGA) database. Read More

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http://dx.doi.org/10.1111/jcmm.15618DOI Listing

Social media usage in family communication about genetic information: 'I no longer speak with my sister but she needed to know'.

J Genet Couns 2020 Jul 9. Epub 2020 Jul 9.

Victorian Clinical Genetics Services, Parkville, Vic., Australia.

The use of social media has become a ubiquitous form of communication. Little is known about whether social media is used in families to assist with the communication of genetic information. This study aimed to understand if and why individuals use social media to communicate genetic information to at-risk relatives. Read More

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http://dx.doi.org/10.1002/jgc4.1307DOI Listing

Genetic counseling following direct-to consumer genetic testing: Consumer perspectives.

J Genet Couns 2020 Jul 9. Epub 2020 Jul 9.

Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.

As the use and scope of direct-to-consumer genetic testing (DTC GT), also becoming known as consumer-driven genetic testing, increases, consumers may seek genetic counseling to understand their results and determine healthcare implications. In this study, we interviewed individuals who sought genetic counseling after receiving DTC GT results to explore their motivations, expectations, and experiences. Participants were recruited from the Impact of Personal Genomics (PGen) Study, a longitudinal cohort study of DTC GT customers. Read More

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http://dx.doi.org/10.1002/jgc4.1309DOI Listing

Disruption of hypoxia-inducible fatty acid binding protein 7 induces beige fat-like differentiation and thermogenesis in breast cancer cells.

Cancer Metab 2020 6;8:13. Epub 2020 Jul 6.

Department of Oncology, Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS UK.

Background: Humans produce heat through non-shivering thermogenesis, a metabolic process that occurs in inducible beige adipocytes expressing uncoupling protein 1 (UCP1). UCP1 dissipates the proton gradient of the mitochondrial inner membrane and converts that energy into heat. It is unclear whether cancer cells can exhibit autonomous thermogenesis. Read More

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http://dx.doi.org/10.1186/s40170-020-00219-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336487PMC

A methylation-based mRNA signature predicts survival in patients with gastric cancer.

Cancer Cell Int 2020 6;20:284. Epub 2020 Jul 6.

Department of Medical Oncology, The First Peoples' Hospital of Wenling City, Wenling, 317500 China.

Background: Evidence suggests that altered DNA methylation plays a causative role in the occurrence, progression and prognosis of gastric cancer (GC). Thus, methylated-differentially expressed genes (MDEGs) could potentially serve as biomarkers and therapeutic targets in GC.

Methods: Four genomics profiling datasets were used to identify MDEGs. Read More

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http://dx.doi.org/10.1186/s12935-020-01374-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336496PMC

A supervised learning framework for chromatin loop detection in genome-wide contact maps.

Nat Commun 2020 Jul 9;11(1):3428. Epub 2020 Jul 9.

Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.

Accurately predicting chromatin loops from genome-wide interaction matrices such as Hi-C data is critical to deepening our understanding of proper gene regulation. Current approaches are mainly focused on searching for statistically enriched dots on a genome-wide map. However, given the availability of orthogonal data types such as ChIA-PET, HiChIP, Capture Hi-C, and high-throughput imaging, a supervised learning approach could facilitate the discovery of a comprehensive set of chromatin interactions. Read More

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http://dx.doi.org/10.1038/s41467-020-17239-9DOI Listing

Inhalation exposure to cigarette smoke and inflammatory agents induces epigenetic changes in the lung.

Sci Rep 2020 Jul 9;10(1):11290. Epub 2020 Jul 9.

Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN, 55455, USA.

Smoking-related lung tumors are characterized by profound epigenetic changes including scrambled patterns of DNA methylation, deregulated histone acetylation, altered gene expression levels, distorted microRNA profiles, and a global loss of cytosine hydroxymethylation marks. Here, we employed an enhanced version of bisulfite sequencing (RRBS/oxRRBS) followed by next generation sequencing to separately map DNA epigenetic marks 5-methyl-dC and 5-hydroxymethyl-dC in genomic DNA isolated from lungs of A/J mice exposed whole-body to environmental cigarette smoke for 10 weeks. Exposure to cigarette smoke significantly affected the patterns of cytosine methylation and hydroxymethylation in the lungs. Read More

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http://dx.doi.org/10.1038/s41598-020-67502-8DOI Listing

HEM1 deficiency disrupts mTORC2 and F-actin control in inherited immunodysregulatory disease.

Science 2020 Jul;369(6500):202-207

Molecular Development of the Immune System Section, Laboratory of Immune System Biology, and Clinical Genomics Program, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.

Immunodeficiency often coincides with hyperactive immune disorders such as autoimmunity, lymphoproliferation, or atopy, but this coincidence is rarely understood on a molecular level. We describe five patients from four families with immunodeficiency coupled with atopy, lymphoproliferation, and cytokine overproduction harboring mutations in , which encodes the hematopoietic-specific HEM1 protein. These mutations cause the loss of the HEM1 protein and the WAVE regulatory complex (WRC) or disrupt binding to the WRC regulator, Arf1, thereby impairing actin polymerization, synapse formation, and immune cell migration. Read More

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http://dx.doi.org/10.1126/science.aay5663DOI Listing

Physical activity does not lower the risk of lung cancer.

Cancer Res 2020 Jul 9. Epub 2020 Jul 9.

Department of Epidemiology and Preventive Medicine, University of Regensburg.

Observational studies have suggested that physical activity might lower the risk of lung can-cer in former and current smokers but not in never smokers. Using genetic instruments for self-reported and accelerometer-measured physical activity traits implemented through two-sample Mendelian randomization (MR), we sought to strengthen the evidence for causality. We used 18 genome-wide significant (P < 5x10-8) single nucleotide polymorphisms (SNP) for self-reported moderate-to-vigorous physical activity and seven SNP for accelerometer-measured ('average acceleration') physical activity from up to 377,234 UK Biobank partici-pants and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell carcinoma and 2,664 small cell carcinoma cases) and 56,450 controls. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-20-1127DOI Listing

Improved Prognostic Prediction in Never-Smoker Lung Cancer Patients by Integration of a Systemic Inflammation Marker with Tumor Immune Contexture Analysis.

Cancers (Basel) 2020 Jul 7;12(7). Epub 2020 Jul 7.

Thoracic Surgery Unit, Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumori, via Venezian 1, 20133 Milan, Italy.

Almost 25% of lung cancers (LCs) occur in never-smokers. LC inflammatory profile, based on plasma C-reactive protein levels (CRP), predicts mortality, independently by smoking-status. We hypothesized that: CRP could be associated with tumor immune contexture (TIC) in never-smokers and both these two parameters may improve their prognosis. Read More

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http://dx.doi.org/10.3390/cancers12071828DOI Listing

Unique Spatial Immune Profiling in Pancreatic Ductal Adenocarcinoma with Enrichment of Exhausted and Senescent T Cells and Diffused CD47-SIRPα Expression.

Cancers (Basel) 2020 Jul 7;12(7). Epub 2020 Jul 7.

Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece.

Background: Pancreatic ductal adenocarcinoma (PDAC) is resistant to single-agent immunotherapies. To understand the mechanisms leading to the poor response to this treatment, a better understanding of the PDAC immune landscape is required. The present work aims to study the immune profile in PDAC in relationship to spatial heterogeneity of the tissue microenvironment (TME) in intact tissues. Read More

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http://dx.doi.org/10.3390/cancers12071825DOI Listing

MicroRNAs as Guardians of the Prostate: Those Who Stand before Cancer. What Do We Really Know about the Role of microRNAs in Prostate Biology?

Int J Mol Sci 2020 Jul 7;21(13). Epub 2020 Jul 7.

Burnett School of Biomedical Sciences, University of Central Florida, Orlando, FL 32816, USA.

Prostate cancer is the second leading cause of cancer-related deaths of men in the Western world. Despite recent advancement in genomics, transcriptomics and proteomics to understand prostate cancer biology and disease progression, castration resistant metastatic prostate cancer remains a major clinical challenge and often becomes incurable. MicroRNAs (miRNAs), about 22-nucleotide-long non-coding RNAs, are a group of regulatory molecules that mainly work through post-transcriptional gene silencing via translational repression. Read More

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http://dx.doi.org/10.3390/ijms21134796DOI Listing

Development of a Genome-Wide Oligonucleotide Microarray Platform for Detection of DNA Copy Number Aberrations in Feline Cancers.

Vet Sci 2020 Jul 7;7(3). Epub 2020 Jul 7.

Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.

The utility of the domestic cat as a model system for biomedical studies was constrained for many years by the absence of a comprehensive feline reference genome sequence assembly. While such a resource now exists, the cat continues to lag behind the domestic dog in terms of integration into the 'One Health' era of molecular medicine. Stimulated by the advances being made within the evolving field of comparative cancer genomics, we developed a microarray platform that allows rapid and sensitive detection of DNA copy number aberrations in feline tumors using comparative genomic hybridization analysis. Read More

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http://dx.doi.org/10.3390/vetsci7030088DOI Listing

A pan-cancer analysis of the oncogenic role of staphylococcal nuclease domain-containing protein 1 (SND1) in human tumors.

Genomics 2020 Jul 6. Epub 2020 Jul 6.

Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; Key Laboratory of Immune Microenvironment and Disease, Ministry of Education, Key Laboratory of Cellular and Molecular Immunology in Tianjin, Excellent Talent Project, Tianjin Medical University, Tianjin, China. Electronic address:

Although emerging cell- or animal-based evidence supports the relationship between SND1 and cancers, no pan-cancer analysis is available. We thus first explored the potential oncogenic roles of SND1 across thirty-three tumors based on the datasets of TCGA (The cancer genome atlas) and GEO (Gene expression omnibus). SND1 is highly expressed in most cancers, and distinct associations exist between SND1 expression and prognosis of tumor patients. Read More

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http://dx.doi.org/10.1016/j.ygeno.2020.06.044DOI Listing

Analysis of relapse-associated alternative mRNA splicing and construction of a prognostic signature predicting relapse in I-III colon cancer.

Genomics 2020 Jul 6. Epub 2020 Jul 6.

Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address:

The literature comprehensively analyzed alternative splicing (AS) events in colon cancer is little and corresponding prognostic signature is still a lack. Based on data of TCGA, the relapse-associated ASs were comprehensively analyzed and a signature was further constructed to predict the relapse in I-III colon cancer. In total 1912 ASs of 1384 mRNA were identified as relapse-associated ASs, protein-protein interactions (PPI) and ASs-splicing factors (SF) interactions network were identified. Read More

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http://dx.doi.org/10.1016/j.ygeno.2020.07.002DOI Listing

Collaborative, Multidisciplinary Evaluation of Cancer Variants Through Virtual Molecular Tumor Boards Informs Local Clinical Practices.

JCO Clin Cancer Inform 2020 Jul;4:602-613

Innovation Center for Biomedical Informatics, Georgetown University Medical Center, Washington, DC.

Purpose: The cancer research community is constantly evolving to better understand tumor biology, disease etiology, risk stratification, and pathways to novel treatments. Yet the clinical cancer genomics field has been hindered by redundant efforts to meaningfully collect and interpret disparate data types from multiple high-throughput modalities and integrate into clinical care processes. Bespoke data models, knowledgebases, and one-off customized resources for data analysis often lack adequate governance and quality control needed for these resources to be clinical grade. Read More

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http://dx.doi.org/10.1200/CCI.19.00169DOI Listing

Sugar-sweetened beverage consumption and risk of hyperuricemia: a longitudinal analysis of the Health Workers Cohort Study participants in Mexico.

Am J Clin Nutr 2020 Jul 9. Epub 2020 Jul 9.

Research Center in Policy, Population, and Health, School of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.

Background: The elevated consumption of sugar-sweetened beverages (SSBs) in Mexico is an important public health concern. However, the association between SSB consumption and hyperuricemia has been scarcely studied and not well documented.

Objectives: To prospectively evaluate the association between SSB consumption and risk of hyperuricemia in Mexican adults. Read More

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http://dx.doi.org/10.1093/ajcn/nqaa160DOI Listing

Rewired signaling network in T cells expressing the chimeric antigen receptor (CAR).

EMBO J 2020 Jul 9:e104730. Epub 2020 Jul 9.

Department of Cell Biology, Yale School of Medicine, New Haven, CT, USA.

The chimeric antigen receptor (CAR) directs T cells to target and kill specific cancer cells. Despite the success of CAR T therapy in clinics, the intracellular signaling pathways that lead to CAR T cell activation remain unclear. Using CD19 CAR as a model, we report that, similar to the endogenous T cell receptor (TCR), antigen engagement triggers the formation of CAR microclusters that transduce downstream signaling. Read More

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http://dx.doi.org/10.15252/embj.2020104730DOI Listing

Corrigendum to: Gene expression profiling of cells of origin of squamous cell carcinomas in head-and-neck, esophagus, and lung.

Acta Biochim Biophys Sin (Shanghai) 2020 Jul 9. Epub 2020 Jul 9.

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

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http://dx.doi.org/10.1093/abbs/gmaa079DOI Listing

Medulloblastoma: an Old Diagnosis with New Promises.

Curr Oncol Rep 2020 Jul 9;22(9):90. Epub 2020 Jul 9.

Department of Pediatrics, Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY, 10065, USA.

Purpose Of Review: Molecular subtyping in medulloblastoma (MB) has diagnostic and prognostic values which impact therapy. This paper provides guidance for the clinician caring for pediatric and adult patients with medulloblastoma in the modern era.

Recent Findings: Medulloblastoma comprises four molecularly distinct subgroups: wingless activated (WNT), sonic hedgehog activated (SHH), group 3, and group 4. Read More

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http://dx.doi.org/10.1007/s11912-020-00953-4DOI Listing

Whole exome sequencing reveals the maintained polyclonal nature from primary to metastatic malignant peripheral nerve sheath tumor in two patients with NF1.

Neurooncol Adv 2020 Jul 10;2(Suppl 1):i75-i84. Epub 2019 Sep 10.

Division of Medical Oncology, Department of Medicine Washington University School of Medicine, St. Louis, Missouri.

Background: Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas with high metastatic rates and poor overall patient survival. There are currently no effective therapies, underscoring the pressing need to define the molecular etiologies that underlie MPNST progression. The aim of this study was to examine clonal progression and identify the molecular events critical for MPNST spread. Read More

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http://dx.doi.org/10.1093/noajnl/vdz026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317063PMC

KIF11 and KIF15 mitotic kinesins are potential therapeutic vulnerabilities for malignant peripheral nerve sheath tumors.

Neurooncol Adv 2020 Jul 4;2(Suppl 1):i62-i74. Epub 2020 Jan 4.

Program of Predictive and Personalized Medicine of Cancer (PMPPC), Germans Trias & Pujol Research Institute (IGTP), Badalona, Barcelona, Spain.

Background: Malignant peripheral nerve sheath tumor (MPNST) constitutes the leading cause of neurofibromatosis type 1-related mortality. MPNSTs contain highly rearranged hyperploid genomes and exhibit a high division rate and aggressiveness. We have studied in vitro whether the mitotic kinesins KIF11, KIF15, and KIF23 have a functional role in maintaining MPNST cell survival and can represent potential therapeutic vulnerabilities. Read More

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http://dx.doi.org/10.1093/noajnl/vdz061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317059PMC

Genetics of human malignant peripheral nerve sheath tumors.

Neurooncol Adv 2020 Jul 28;2(Suppl 1):i50-i61. Epub 2019 Nov 28.

Division of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts.

Malignant peripheral nerve sheath tumors (MPNSTs) are heterogeneous, highly aggressive tumors with no widely effective treatment other than surgery. Genomic architecture of MPNST is similar to other soft tissue sarcomas, with a relatively modest burden of single nucleotide variants and an elevated frequency of copy-number alterations. Recent advances in genomic studies identified previously unrecognized critical involvement of polycomb repressor complex 2 (PRC2) core components and in transition to malignancy. Read More

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http://dx.doi.org/10.1093/noajnl/vdz049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317054PMC

Proteins inform survival-based differences in patients with glioblastoma.

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa039. Epub 2020 Mar 17.

Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.

Background: Improving the care of patients with glioblastoma (GB) requires accurate and reliable predictors of patient prognosis. Unfortunately, while protein markers are an effective readout of cellular function, proteomics has been underutilized in GB prognostic marker discovery.

Methods: For this study, GB patients were prospectively recruited and proteomics discovery using liquid chromatography-mass spectrometry analysis (LC-MS/MS) was performed for 27 patients including 13 short-term survivors (STS) (≤10 months) and 14 long-term survivors (LTS) (≥18 months). Read More

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http://dx.doi.org/10.1093/noajnl/vdaa039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212893PMC

Gliomas display distinct sex-based differential methylation patterns based on molecular subtype.

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa002. Epub 2020 Jan 8.

Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.

Background: Gliomas are the most common type of primary brain tumor and one of many cancers where males are diagnosed with greater frequency than females. However, little is known about the sex-based molecular differences in glioblastomas (GBMs) or lower grade glioma (non-GBM) subtypes. DNA methylation is an epigenetic mechanism involved in regulating gene transcription. Read More

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http://dx.doi.org/10.1093/noajnl/vdaa002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212920PMC
January 2020

Sexually dimorphic impact of the iron-regulating gene, , on survival in glioblastoma.

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa001. Epub 2020 Feb 17.

Department of Neurosurgery, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.

Background: The median survival for patients with glioblastoma (GBM), the most common primary malignant brain tumor in adults, has remained approximately 1 year for more than 2 decades. Recent advances in the field have identified GBM as a sexually dimorphic disease. It is less prevalent in females and they have better survival compared to males. Read More

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http://dx.doi.org/10.1093/noajnl/vdaa001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212901PMC
February 2020

Involvement of hepatic lipid droplets and their associated proteins in the detoxification of aflatoxin B in aflatoxin-resistance BALB/C mouse.

Toxicol Rep 2020 22;7:795-804. Epub 2020 Jun 22.

Department of Molecular Biology and Biotechnology, Atomic Energy Commission of Syria (AECS), P.O. Box 6091, Damascus, Syria.

The highly potent carcinogen, Aflatoxin B, induces liver cancer in many animals including humans but some mice strains are highly resistant. This murine resistance is due to a rapid detoxification of AFB. Hepatic lipid droplets (LDs) ultimately impact the liver functions but their potential role in AFB detoxification has not been addressed. Read More

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http://dx.doi.org/10.1016/j.toxrep.2020.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334552PMC

Pharmacophore-based virtual screening for the identification of the novel Src inhibitor SJG-136 against lung cancer cell growth and motility.

Am J Cancer Res 2020 1;10(6):1668-1690. Epub 2020 Jun 1.

Institute of Biomedical Sciences, National Chung Hsing University Taichung, Taiwan.

Aberrant elevated Src activity is related to lung cancer growth and metastasis. Therefore, the development of potent small molecule inhibitors to target Src kinase is a potential therapeutic strategy for lung cancer. This study aimed to develop a computational model for the in silico screening of Src inhibitors and then assess the suppressive effect of candidate compounds on cellular functions. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339285PMC