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Precision medicine genomics

Sun-Young Lee, Sery Lim, Dong-Hyu Cho
A 16-year-old female with Ewing sarcoma, a very rare disease with poor prognosis in women, was admitted to the hospital with abdominal pain. Diagnostic laparotomy revealed the Ewing sarcoma originating from the extramural uterus. Histological examination yielded positive test results for CD99, vimentin, S-100, eosin 5-maleimide and periodic acid-Shiff. EWS-FLI1 type 1 translocation was confirmed. Fibroblast growth factor receptor (FGFR) 4 (c.1162G> A) and HRas proto-oncogene (HRAS; c.182A> G) mutations were also detected...
August 2018: Experimental and Therapeutic Medicine
Stephen P Robertson, Jennie Harre Hindmarsh, Sarah Berry, Vicky A Cameron, Murray P Cox, Ofa Dewes, Robert N Doughty, George Gray, Jessie C Jacobsen, Albert Laurence, Elizabeth Matisoo-Smith, Susan Morton, Andrew N Shelling, Dianne Sika-Paotonu, Anna Rolleston, Jonathan R Skinner, Russell G Snell, Andrew Sporle, Cristin Print, Tony R Merriman, Maui Hudson, Philip Wilcox
Precision medicine seeks to draw on data from both individuals and populations across disparate domains to influence and support diagnosis, management and prevention in healthcare at the level of the individual patient and their family/whānau. Central to this initiative is incorporating the effects of the inherent variation that lies within genomes and can influence health outcomes. Identifying and interpreting such variation requires an accurate, valid and representative dataset to firstly define what variants are present and then assess the potential relevance for the health of a person, their family/whānau and the wider community to which they belong...
August 17, 2018: New Zealand Medical Journal
Juliane Lippert, Silke Appenzeller, Raimunde Liang, Silviu Sbiera, Stefan Kircher, Barbara Altieri, Indrajit Nanda, Isabel Weigand, Andrea Gehrig, Sonja Steinhauer, Renzo J M Riemens, Andreas Rosenwald, Clemens R Müller, Matthias Kroiss, Simone Rost, Martin Fassnacht, Cristina L Ronchi
Context: Adrenocortical carcinoma (ACC) has a heterogeneous prognosis and current medical therapies have limited efficacy in its advanced stages. Genome-wide multi-omics-studies identified molecular patterns associated with clinical outcome. Objective: Here, we aimed at identifying a molecular signature useful for both personalized prognostic stratification and druggable targets, using methods applicable in clinical routine. Design: 117 tumor samples from 107 ACC patients were analyzed...
August 2, 2018: Journal of Clinical Endocrinology and Metabolism
Jorge I Vélez, Francisco Lopera, Penelope K Creagh, Laura B Piñeros, Debjani Das, Martha L Cervantes-Henríquez, Johan E Acosta-López, Mario A Isaza-Ruget, Lady G Espinosa, Simon Easteal, Gustavo A Quintero, Claudia Tamar Silva, Claudio A Mastronardi, Mauricio Arcos-Burgos
The identification of novel genetic variants contributing to the widespread in the age of onset (AOO) of Alzheimer's disease (AD) could aid in the prognosis and/or development of new therapeutic strategies focused on early interventions. We recruited 78 individuals with AD from the Paisa genetic isolate in Antioquia, Colombia. These individuals belong to the world largest multigenerational and extended pedigree segregating AD as a consequence of a dominant fully penetrant mutation in the PSEN1 gene and exhibit an AOO ranging from the early 1930s to the late 1970s...
August 15, 2018: Molecular Neurobiology
Kuo Liu, Wei Yu, Muxue Tang, Juan Tang, Xiuxiu Liu, Qiaozhen Liu, Yan Li, Lingjuan He, Libo Zhang, Sylvia M Evans, Xueying Tian, Kathy O Lui, Bin Zhou
In vivo genomic engineering is instrumental for studying developmental biology and regenerative medicine. Development of novel systems with more site-specific recombinases (SSRs) that complement with the commonly used Cre-loxP would be valuable for more precise lineage tracing and genome editing. Here we introduce a new SSR system via Nigri-nox. By generating tissue-specific Nigri knock-in and its responding nox reporter mice, we show that Nigri-nox system works efficiently in vivo by targeting specific tissues...
August 15, 2018: Development
Yan-Bin Pang, Ping Wu, Luo-Ming Hua, Xin DU, Jing Wang
The myelodysplastic syndromes (MDS) are a heterogeneous group of clonal myeloid disorders characterized by ineffective hematopoiesis and increased risk of transformation to acute myelogenous leukemia (AML). The treatment of MDS is highly dependent on the reliability of the prognostic evaluation model. Current clinical prognostic scoring systems are comprised of morphology, pivotal clinical trials and cytogenetic findings. However, none of the available prognostic systems incorporates disease-related molecular abnormalities, such as somatic mutations...
August 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Imke H Bartelink, Ella F Jones, Sheerin K Shahidi-Latham, Evelyn Lee Pei Rong, Yanan Zheng, Paolo Vicini, Laura van 't Veer, Denise Wolf, Andrei Iagaru, Deanna L Kroetz, Brendan Prideaux, Cornelius Cilliers, Greg Thurber, Zena Wimana, Geraldine Gebhart
Precision medicine aims to use patient genomic, epigenomic, specific drug dose and other data to define disease patterns that may potentially lead to an improved treatment outcome. Personalized dosing regimens based on tumor drug penetration can play a critical role in this approach. State-of-the-art techniques to measure tumor drug penetration focus on systemic exposure, tissue penetration, cellular or molecular engagement and expression of pharmacological activity. Using In silico methods, this information can be integrated to bridge the gap between the therapeutic regimen and the pharmacological link with clinical outcome...
August 14, 2018: Clinical Pharmacology and Therapeutics
Hang Wang, Jianing Xi, Minghui Wang, Ao Li
An effective way to facilitate the development of modern oncology precision medicine is the systematical analysis of the known drug sensitivities that have emerged in recent years. Meanwhile, the screening of drug response in cancer cell lines provides an estimable genomic and pharmacological data towards high accuracy prediction. Existing works primarily utilize genomic or functional genomic features to classify or regress the drug response. Here in this work, by the migration and extension of the conventional merchandise recommendation methods, we introduce an innovation model on accurate drug sensitivity prediction by using dual-layer strengthened collaborative topic regression (DS-CTR), which incorporates not only the graphic model to jointly learn drugs and cell lines feature from pharmacogenomics data but also drug and cell line similarity network model to strengthen the correlation of the prediction results...
August 10, 2018: IEEE/ACM Transactions on Computational Biology and Bioinformatics
Jean-Louis Pujol, Benoît Roch, Camille N Pujol, Catherine Goze
Small cell lung cancer accounts for 14% of all lung cancers. It remains a major challenge for oncology as the progresses made in the past three decades are modest. After a rapid overview of current knowledge regarding somatic genomic alterations, this state-of-art addresses pathways to improve small-cell lung cancer outcome such as the targeting of DNA damage repair mechanisms firstly anti-PARPs, inhibitory molecules of EZH2, derepression of the NOTCH pathway, rovalbituzumab-tesirine, inhibition of serine/threonine Aurora A kinase, temozolomide and its dependence on methylation of the MGMT promoter...
August 9, 2018: Bulletin du Cancer
Megan M Niedzwiecki, Douglas I Walker, Roel Vermeulen, Marc Chadeau-Hyam, Dean P Jones, Gary W Miller
Derived from the term exposure, the exposome is an omic-scale characterization of the nongenetic drivers of health and disease. With the genome, it defines the phenome of an individual. The measurement of complex environmental factors that exert pressure on our health has not kept pace with genomics and historically has not provided a similar level of resolution. Emerging technologies make it possible to obtain detailed information on drugs, toxicants, pollutants, nutrients, and physical and psychological stressors on an omic scale...
August 10, 2018: Annual Review of Pharmacology and Toxicology
Raymond G De Vries, Kerry A Ryan, Linda Gordon, Chris D Krenz, Tom Tomlinson, Scott Jewell, Scott Y H Kim
Do members of the public believe that biobanks should accommodate the moral concerns of donors about the types of research done with their biospecimens? The answer to this question is critical to the future of genomic and precision medicine, endeavors that rely on a public willing to share their biospecimens and medical data. To explore public attitudes regarding the requirements of consent for biobank donations, we organized three democratic deliberations involving 180 participants. The deliberative sessions involved small group discussions informed by presentations given by experts in both biobank research and ethics...
August 10, 2018: Qualitative Health Research
Juan Jovel, Zhen Lin, Sandra O'keefe, Steven Willows, Weiwei Wang, Guangzhi Zhang, Jordan Patterson, Carlos Moctezuma-Velázquez, David J Kelvin, Gane Ka-Shu Wong, Andrew L Mason
Understanding the heterogeneity of dysregulated pathways associated with the development of hepatocellular carcinoma (HCC) may provide prognostic and therapeutic avenues for disease management. As HCC involves a complex process of genetic and epigenetic modifications, we evaluated expression of both polyadenylated transcripts and microRNAs from HCC and liver samples derived from two cohorts of patients undergoing either partial hepatic resection or liver transplantation. Copy number variants were inferred from whole genome low-pass sequencing data, and a set of 56 cancer-related genes were screened using an oncology panel assay...
August 2018: Hepatology Communications
Sung Noh Hong
Colorectal cancer (CRC) arise from multi-step carcinogenesis due to genetic mutations and epigenetic modifications of human genome. Genetic mutations and epigenetic modifications were originally established as 2 independent mechanisms contributing to colorectal carcinogenesis. However, recent evidences demonstrate that there are interactions between these 2 mechanisms. Genetic mutations enable disruption of epigenetic controls while epigenetic modifications can initiate genomic instability and carcinogenesis...
July 2018: Intestinal Research
Oz Mordechai, Myriam Weyl-Ben-Arush
OBJECTIVE: To date, the understanding of pediatric tumor genomics and how these genetic aberrations correlate with clinical outcome is lacking. Here, we report our experience with the next-generation sequencing (NGS) test program and discuss implications for the inclusion of molecular profiling into clinical pediatric oncology trials. We also aimed to explore studies on NGS in pediatric cancers and to quantify the variability of finding actionable mutations and the clinical implications...
July 30, 2018: Rambam Maimonides Medical Journal
Laura Muinelo-Romay, Carlos Casas-Arozamena, Miguel Abal
The identification of new molecular targets and biomarkers associated with high risk of recurrence and response to therapy represents one of the main clinical challenges in the management of advanced disease in endometrial cancer. In this sense, the field of liquid biopsy has emerged as a great revolution in oncology and is considered "the way" to reach personalised medicine. In this review, we discuss the promising but already relatively limited advances of liquid biopsy in endometrial cancer compared to other types of tumours like breast, colorectal or prostate cancer...
August 7, 2018: International Journal of Molecular Sciences
C-A Azencott
Machine learning can have a major societal impact in computational biology applications. In particular, it plays a central role in the development of precision medicine, whereby treatment is tailored to the clinical or genetic features of the patient. However, these advances require collecting and sharing among researchers large amounts of genomic data, which generates much concern about privacy. Researchers, study participants and governing bodies should be aware of the ways in which the privacy of participants might be compromised, as well as of the large body of research on technical solutions to these issues...
September 13, 2018: Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences
Jeffrey B Kopp, Cheryl A Winkler
Recent advances in genetics of renal disease have deepened our understanding of progressive kidney disease. Here, we review genetic variants that are of particular importance to progressive glomerular disease that result in end-stage kidney disease (ESKD). Some of the most striking findings relate to APOL1 genetic variants, seen exclusively in individuals of sub-Saharan African descent, that create a predisposition to particular renal disorders, including focal segmental glomerulosclerosis and arterionephrosclerosis...
July 2018: Seminars in Nephrology
Chad J Creighton
Knowledge of the molecular subtypes of bladder cancer enables powerful generalizations involving the distinctive biology and pathways driving different disease subsets. Areas Covered: In this review, we summarize the findings of a number of published studies exploring the molecular landscape of bladder cancer by analysis of genomic data from The Cancer Genome Atlas (TCGA). TCGA project has provided a comprehensive data resource of 412 muscle-invasive bladder cancers as characterized by multiple molecular analytical platforms...
August 6, 2018: Expert Review of Anticancer Therapy
Stephen M Modell, Toby Citrin, Sharon L R Kardia
The United States Precision Medicine Initiative (PMI) was announced by then President Barack Obama in January 2015. It is a national effort designed to take into account genetic, environmental, and lifestyle differences in the development of individually tailored forms of treatment and prevention. This goal was implemented in March 2015 with the formation of an advisory committee working group to provide a framework for the proposed national research cohort of one million or more participants. The working group further held a public workshop on participant engagement and health equity, focusing on the design of an inclusive cohort, building public trust, and identifying active participant engagement features for the national cohort...
August 3, 2018: Healthcare (Basel, Switzerland)
Kristie N Ramos, Irma N Ramos, Yi Zeng, Kenneth S Ramos
Pediatric leukemia represents a heterogeneous group of diseases characterized by germline and somatic mutations that manifest within the context of disturbances in the epigenetic machinery and genetic regulation. Advances in genomic medicine have allowed finer resolution of genetic and epigenetic strategies that can be effectively used to risk-stratify patients and identify novel targets for therapy. This review discusses the genetic and epigenetic mechanisms of leukemogenesis, particularly as it relates to acute lymphocytic leukemias, the mechanisms of epigenetic control of leukemogenesis, namely DNA methylation, histone modifications, microRNAs, and LINE-1 retroelements, and highlights opportunities for precision medicine therapeutics in further guiding disease management...
2018: F1000Research
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