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José E Belizário, Beatriz A Sangiuliano, Marcela Perez-Sosa, Jennifer M Neyra, Dayson F Moreira
With multiple omics strategies being applied to several cancer genomics projects, researchers have the opportunity to develop a rational planning of targeted cancer therapy. The investigation of such numerous and diverse pharmacogenomic datasets is a complex task. It requires biological knowledge and skills on a set of tools to accurately predict signaling network and clinical outcomes. Herein, we describe Web-based in silico approaches user friendly for exploring integrative studies on cancer biology and pharmacogenomics...
2016: Frontiers in Pharmacology
Kimberly Maxfield, Jennifer Macion, Hariprasad Vankayalapati, Angelique W Whitehurst
Triple negative breast cancer (TNBC) is a highly heterogeneous disease with multiple, distinct molecular subtypes that exhibit unique transcriptional programs and clinical progression trajectories. Despite knowledge of the molecular heterogeneity of the disease, most patients are limited to generic, indiscriminate treatment options: cytotoxic chemotherapy, surgery and radiation. To identify new intervention targets in TNBC, we used large-scale, loss of function screening to identify molecular vulnerabilities among different oncogenomic backgrounds...
October 3, 2016: Molecular and Cellular Biology
Nathan Bucay, Kirandeep Sekhon, Shahana Majid, Soichiro Yamamura, Varahram Shahryari, Z Laura Tabatabai, Kirsten Greene, Yuichiro Tanaka, Rajvir Dahiya, Guoren Deng, Sharanjot Saini
Genomic loss of chromosome (chr) 8p21 region, containing prostate-specific NKX3.1 gene, is a frequent alteration of the prostate cancer (PCa) oncogenome. We propose a novel, paradigm shifting hypothesis that this frequently deleted locus is also associated with a cluster of microRNA genes- miR-3622a/b- that are lost in PCa and play an important mechanistic role in progression and metastasis. In this study, we demonstrate the role of miR-3622b in prostate cancer. Expression analyses in a cohort of PCa clinical specimens and cell lines show that miR-3622b expression is frequently lost in prostate cancer...
September 6, 2016: Oncotarget
Richard M White
The zebrafish has emerged as an important model for studying cancer biology. Identification of DNA, RNA and chromatin abnormalities can give profound insight into the mechanisms of tumorigenesis and the there are many techniques for analyzing the genomes of these tumors. Here, I present an overview of the available technologies for analyzing tumor genomes in the zebrafish, including array based methods as well as next-generation sequencing technologies. I also discuss the ways in which zebrafish tumor genomes can be compared to human genomes using cross-species oncogenomics, which act to filter genomic noise and ultimately uncover central drivers of malignancy...
2016: Advances in Experimental Medicine and Biology
Janessa Laskin, Steven Jones, Samuel Aparicio, Stephen Chia, Carolyn Ch'ng, Rebecca Deyell, Peter Eirew, Alexandra Fok, Karen Gelmon, Cheryl Ho, David Huntsman, Martin Jones, Katayoon Kasaian, Aly Karsan, Sreeja Leelakumari, Yvonne Li, Howard Lim, Yussanne Ma, Colin Mar, Monty Martin, Richard Moore, Andrew Mungall, Karen Mungall, Erin Pleasance, S Rod Rassekh, Daniel Renouf, Yaoqing Shen, Jacqueline Schein, Kasmintan Schrader, Sophie Sun, Anna Tinker, Eric Zhao, Stephen Yip, Marco A Marra
Given the success of targeted agents in specific populations it is expected that some degree of molecular biomarker testing will become standard of care for many, if not all, cancers. To facilitate this, cancer centers worldwide are experimenting with targeted "panel" sequencing of selected mutations. Recent advances in genomic technology enable the generation of genome-scale data sets for individual patients. Recognizing the risk, inherent in panel sequencing, of failing to detect meaningful somatic alterations, we sought to establish processes to integrate data from whole-genome analysis (WGA) into routine cancer care...
October 2015: Cold Spring Harbor Molecular Case Studies
M R Jones, K A Schrader, Y Shen, E Pleasance, C Ch'ng, N Dar, S Yip, D J Renouf, J E Schein, A J Mungall, Y Zhao, R Moore, Y Ma, B S Sheffield, T Ng, S J M Jones, M A Marra, J Laskin, H J Lim
BACKGROUND: A patient suffering from metastatic colorectal cancer, treatment-related toxicity and resistance to standard chemotherapy and radiation was assessed as part of a personalized oncogenomics initiative to derive potential alternative therapeutic strategies. PATIENTS AND METHODS: Whole-genome and transcriptome sequencing was used to interrogate a metastatic tumor refractory to standard treatments of a patient with mismatch repair-deficient metastatic colorectal cancer...
May 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Haruna Takeda, Alistair G Rust, Jerrold M Ward, Christopher Chin Kuan Yew, Nancy A Jenkins, Neal G Copeland
Mutations in SMAD4 predispose to the development of gastrointestinal cancer, which is the third leading cause of cancer-related deaths. To identify genes driving gastric cancer (GC) development, we performed a Sleeping Beauty (SB) transposon mutagenesis screen in the stomach of Smad4(+/-) mutant mice. This screen identified 59 candidate GC trunk drivers and a much larger number of candidate GC progression genes. Strikingly, 22 SB-identified trunk drivers are known or candidate cancer genes, whereas four SB-identified trunk drivers, including PTEN, SMAD4, RNF43, and NF1, are known human GC trunk drivers...
April 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
Henry Sung-Ching Wong, Yung-Shun Juan, Mei-Shin Wu, Yan-Feng Zhang, Yu-Wen Hsu, Huang-Hui Chen, Wei-Min Liu, Wei-Chiao Chang
A major challenge in personalized cancer medicine is to establish a systematic approach to translate huge oncogenomic datasets to clinical situations and facilitate drug discovery for cancers such as endometrial carcinoma. We performed a genome-wide somatic mutation-expression association study in a total of 219 endometrial cancer patients from TCGA database, by evaluating the correlation between ~5,800 somatic mutations to ~13,500 gene expression levels (in total, ~78, 500, 000 pairs). A bioinformatics pipeline was devised to identify expression-associated single nucleotide variations (eSNVs) which are crucial for endometrial cancer progression and patient prognoses...
February 2, 2016: Oncotarget
Fotini M Kouri, Carissa Ritner, Alexander H Stegh
Glioblastoma (GBM) is an incurable cancer, with survival rates of just 14-16 months after diagnosis. (1) Functional genomics have identified numerous genetic events involved in GBM development. One of these, the deregulation of microRNAs (miRNAs), has been attracting increasing attention due to the multiple biologic processes that individual miRNAs influence. Our group has been studying the role of miR-182 in GBM progression, therapy resistance, and its potential as GBM therapeutic. Oncogenomic analyses revealed that miR-182 is the only miRNA, out of 470 miRNAs profiled by The Cancer Genome Atlas (TCGA) program, which is associated with favorable patient prognosis, neuro-developmental context, temozolomide (TMZ) susceptibility, and most significantly expressed in the least aggressive oligoneural subclass of GBM...
2015: Cell Cycle
George Miles, James Rae, Suresh S Ramalingam, John Pfeifer
Personalized oncology, or more aptly precision oncogenomics, refers to the identification and implementation of clinically actionable targets tailored to an individual patient's cancer genomic information. Banking of human tissue and other biospecimens establishes a framework to extract and collect the data essential to our understanding of disease pathogenesis and treatment. Cancer cooperative groups in the United States have led the way in establishing robust biospecimen collection mechanisms to facilitate translational research, and combined with technological advances in molecular testing, tissue banking has expanded from its traditional base in academic research and is assuming an increasingly pivotal role in directing the clinical care of cancer patients...
October 2015: Seminars in Oncology
Wessel N van Wieringen, Aad W van der Vaart
Many pathways are dysregulated in cancer. Dysregulation of the regulatory network results in less control of transcript levels in the cell. Hence, dysregulation is reflected in the heterogeneity of the transcriptome: the more dysregulated the pathway, the more the transcriptomic heterogeneity. We identify four scenarios for a transcriptomic heterogeneity increase (i.e., pathway dysregulation) in cancer: (1) activation of a molecular switch, (2) a structural change in a regulator, (3) a temporal change in a regulator, and (4) weakening of gene-gene interactions...
September 2015: Bulletin of Mathematical Biology
Hem D Shukla, Javed Mahmood, Zeljko Vujaskovic
Cancer is the leading cause of mortality among men and women worldwide. Despite the availability of numerous diagnostic techniques for various cancers, the overall survival rate remains low and the majority of patients die due to late diagnosis and advanced stage of the disease. Diagnosing and treating cancer at its early stages ideally during the precancerous phase could significantly increase survival rate with the possibility of cure and prolong survival. Cancer is a genetic disease and it is illicitly activated by the acquisition of somatic DNA lesions and aberrations in genome structure and defects in maintenance and repair...
December 1, 2015: Cancer Letters
Jens U Marquardt, Jesper B Andersen
Primary liver cancers are among the most rapidly evolving malignant tumors worldwide. An underlying chronic inflammatory liver disease, which precedes liver cancer development for several decades and frequently creates a pro-oncogenic microenvironment, impairs progress in therapeutic approaches. Molecular heterogeneity of liver cancer is potentiated by a crosstalk between epithelial tumor and stromal cells that complicate translational efforts to unravel molecular mechanisms of hepatocarcinogenesis with a drugable intend...
2015: Hepatic Oncology
Jianfeng Guo, Sharon L McKenna, Michael E O'Dwyer, Mary R Cahill, Caitriona M O'Driscoll
INTRODUCTION: Multiple myeloma (MM) is a hematological malignancy characterized by infiltration of malignant plasma cells in the bone marrow (BM) and end-organ damage to the bone, BM, kidney and immune system. Although current treatments have improved the treatment of MM, it still remains an incurable disease. RNA interference (RNAi) effectors such as microRNAs and small interference RNAs have shown potential to selectively downregulate genes implicated in the pathology of a range of diseases...
2016: Expert Opinion on Therapeutic Targets
Nilotpal Chowdhury, Shantanu Sapru
INTRODUCTION: Microarray analysis has revolutionized the role of genomic prognostication in breast cancer. However, most studies are single series studies, and suffer from methodological problems. We sought to use a meta-analytic approach in combining multiple publicly available datasets, while correcting for batch effects, to reach a more robust oncogenomic analysis. AIM: The aim of the present study was to find gene sets associated with distant metastasis free survival (DMFS) in systemically untreated, node-negative breast cancer patients, from publicly available genomic microarray datasets...
2015: PloS One
Richard M White
The zebrafish is a relatively recent addition to cancer modeling. These models have now been extensively used in cross-species oncogenomic analyses at both the DNA and RNA levels. The goal of such studies is to identify conserved events that occur in both human and fish tumors which may act as central drivers of tumor phenotypes. Numerous comparisons of somatic DNA changes, using array CGH and exome sequencing, have demonstrated a relatively small set of conserved changes across species. In contrast, striking conservation of RNA expression patterns have been observed between the two species in models such as melanoma, leukemia, and rhabdomyosarcoma...
February 2015: Current Opinion in Genetics & Development
Anja Mottok, Christian Steidl
PURPOSE OF REVIEW: Malignant lymphomas represent a remarkably heterogeneous group of cancers with respect to their oncogenome, phenotype and clinical presentation. Lymphoma cells benefit from limited immune surveillance and have developed various mechanisms to alter antitumor immune responses. This article summarizes our current knowledge about genomic alterations underlying acquired immune privilege in lymphoid cancers. RECENT FINDINGS: The implementation and broad application of next-generation sequencing techniques have significantly expanded our knowledge about genetic alterations and perturbed cellular pathways underlying lymphomagenesis...
July 2015: Current Opinion in Hematology
Jason K Sa, Yeup Yoon, Misuk Kim, Yeonghwan Kim, Hee Jin Cho, Jin-Ku Lee, Gi-Soo Kim, Suji Han, Woon Jin Kim, Yong Jae Shin, Kyeung Min Joo, Patrick J Paddison, Tohru Ishitani, Jeongwu Lee, Do-Hyun Nam
Glioblastoma (GBM) is the most lethal brain cancer with profound genomic alterations. While the bona fide tumor suppressor genes such as PTEN, NF1, and TP53 have high frequency of inactivating mutations, there may be the genes with GBM-suppressive roles for which genomic mutation is not a primary cause for inactivation. To identify such genes, we employed in vivo RNAi screening approach using the patient-derived GBM xenograft models. We found that Nemo-Like Kinase (NLK) negatively regulates mesenchymal activities, a characteristic of aggressive GBM, in part via inhibition of WNT/β-catenin signaling...
August 21, 2015: Oncotarget
Vincent Gardeux, Rachid Chelouah, Maria F Barbosa Wanderley, Patrick Siarry, Antônio P Braga, Fabien Reyal, Roman Rouzier, Lajos Pusztai, René Natowicz
BACKGROUND: Filter feature selection methods compute molecular signatures by selecting subsets of genes in the ranking of a valuation function. The motivations of the valuation functions choice are almost always clearly stated, but those for selecting the genes according to their ranking are hardly ever explicit. METHOD: We addressed the computation of molecular signatures by searching the optima of a bi-objective function whose solution space was the set of all possible molecular signatures, ie, the set of subsets of genes...
2015: Cancer Informatics
Tsung-Jung Wu, Lynn M Schriml, Qing-Rong Chen, Maureen Colbert, Daniel J Crichton, Richard Finney, Ying Hu, Warren A Kibbe, Heather Kincaid, Daoud Meerzaman, Elvira Mitraka, Yang Pan, Krista M Smith, Sudhir Srivastava, Sari Ward, Cheng Yan, Raja Mazumder
Bio-ontologies provide terminologies for the scientific community to describe biomedical entities in a standardized manner. There are multiple initiatives that are developing biomedical terminologies for the purpose of providing better annotation, data integration and mining capabilities. Terminology resources devised for multiple purposes inherently diverge in content and structure. A major issue of biomedical data integration is the development of overlapping terms, ambiguous classifications and inconsistencies represented across databases and publications...
2015: Database: the Journal of Biological Databases and Curation
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