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Search Results: 1 - 10 of 386 matches for " Kristine Kleivi "
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Advances in the genetics and epigenetics of gene regulation and human disease
Kristine Kleivi
Genome Biology , 2006, DOI: 10.1186/gb-2006-7-8-325
Abstract: At the recent annual meeting on the human genome in Helsinki, organized by the Human Genome Organisation (HUGO), close to 700 scientists gathered to present and discuss the latest advances in genome research. This report presents some selected highlights.Through their effects on gene expression, polymorphisms in the human genome can contribute to phenotypic variation and disease susceptibility. For many diseases, such as cancer, great effort is being made to study the sequence variants that contribute to disease susceptibility. The impact of genetic variation on common diseases was addressed by Kari Stefansson (deCODE Genetics, Reykjavik, Iceland), who gave an update on the identified sequence variants that may increase the risk of developing type 2 diabetes, prostate cancer, myocardial infarction, stroke and schizophrenia. In the past decades, type 2 diabetes has become a major health problem in the Western world, as both its incidence and its prevalence have increased rapidly. Stefansson reported his group's recent discovery of an inherited variant of the gene TCF7L7, encoding a protein called transcription factor 7-like 2 located on chromosome 10, which is estimated to account for about 20% of the diabetes cases. They have also showed an association between a common genetic variant in the microsatellite DG8S737 at chromosome band 8q24, which may contribute to the development of prostate cancers in European and African populations.Single-nucleotide polymorphism (SNP) genotypes correlated with gene-expression data in breast tumors were presented by Vessela Kristensen (The Norwegian Radium Hospital, Oslo, Norway). For genotyping, she and her colleagues selected sets of genes involved in reactive oxygen species signaling (ROS) and the repair of DNA damage caused by ROS - that is, pathways that are generally affected by chemotherapy and radiation therapy. Using various statistical approaches, the genetic association between SNPs in genes involved in the ROS pathways a
Data integration from two microarray platforms identifies bi-allelic genetic inactivation of RIC8A in a breast cancer cell line
Aslaug Muggerud, Henrik Edgren, Maija Wolf, Kristine Kleivi, Emelyne Dejeux, J?rg Tost, Therese S?rlie, Olli Kallioniemi
BMC Medical Genomics , 2009, DOI: 10.1186/1755-8794-2-26
Abstract: We integrated here genome-wide copy number data with gene expression data and non-sense mediated mRNA decay rates in breast cancer cell lines to prioritize gene candidates that are likely to be tumour suppressor genes inactivated by bi-allelic genetic events. The candidates were sequenced to identify potential mutations.This integrated genomic approach led to the identification of RIC8A at 11p15 as a putative candidate target gene for the genomic deletion in the ZR-75-1 breast cancer cell line. We identified a truncating mutation in this cell line, leading to loss of expression and rapid decay of the transcript. We screened 127 breast cancers for RIC8A mutations, but did not find any pathogenic mutations. No promoter hypermethylation in these tumours was detected either. However, analysis of gene expression data from breast tumours identified a small group of aggressive tumours that displayed low levels of RIC8A transcripts. qRT-PCR analysis of 38 breast tumours showed a strong association between low RIC8A expression and the presence of TP53 mutations (P = 0.006).We demonstrate a data integration strategy leading to the identification of RIC8A as a gene undergoing a classical double-hit genetic inactivation in a breast cancer cell line, as well as in vivo evidence of loss of RIC8A expression in a subgroup of aggressive TP53 mutant breast cancers.Identification of genetic events that are involved in the development of human cancer has been facilitated by the availability of advanced genomic microarray platforms [1]. However, often the mechanisms by which these genetic events influence target genes in the chromosomal regions affected and eventually on the tumourigenic process, remain unknown. Altered genomic regions identified by e.g. array-based comparative genomic hybridization (aCGH), may contain hundreds of candidate genes making the identification of specific disease-causing changes challenging. We have recently applied nonsense-mediated mRNA decay (NMD) microar
High-Throughput 3D Screening Reveals Differences in Drug Sensitivities between Culture Models of JIMT1 Breast Cancer Cells
Vesa Hongisto, Sandra Jernstr?m, Vidal Fey, John-Patrick Mpindi, Kristine Kleivi Sahlberg, Olli Kallioniemi, Merja Per?l?
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0077232
Abstract: The traditional method for studying cancer in vitro is to grow immortalized cancer cells in two-dimensional monolayers on plastic. However, many cellular features are impaired in these artificial conditions, and large changes in gene expression compared to tumors have been reported. Three-dimensional cell culture models have become increasingly popular and are suggested to be better models than two-dimensional monolayers due to improved cell-to-cell contact and structures that resemble in vivo architecture. The aim of this study was to develop a simple high-throughput three-dimensional drug screening method and to compare drug responses in JIMT1 breast cancer cells when grown in two dimensions, in poly(2-hydroxyethyl methacrylate) induced anchorage-independent three-dimensional models, and in Matrigel three-dimensional cell culture models. We screened 102 compounds with multiple concentrations and biological replicates for their effects on cell proliferation. The cells were either treated immediately upon plating, or they were allowed to grow in three-dimensional cultures for 4 days before the drug treatment. Large variations in drug responses were observed between the models indicating that comparisons of culture model-influenced drug sensitivities cannot be made based on the effects of a single drug. However, we show with the 63 most prominent drugs that, in general, JIMT1 cells grown on Matrigel were significantly more sensitive to drugs than cells grown in two-dimensional cultures, while the responses of cells grown in poly(2-hydroxyethyl methacrylate) resembled those of the two-dimensional cultures. Furthermore, comparing the gene expression profiles of the cell culture models to xenograft tumors indicated that cells cultured in Matrigel and as xenografts most closely resembled each other. In this study, we also suggest that three-dimensional cultures can provide a platform for systematic experimentation of larger compound collections in a high-throughput mode and be used as alternatives to traditional two-dimensional screens for better comparability to the in vivo state.
Identification of fusion genes in breast cancer by paired-end RNA-sequencing
Henrik Edgren, Astrid Murumagi, Sara Kangaspeska, Daniel Nicorici, Vesa Hongisto, Kristine Kleivi, Inga H Rye, Sandra Nyberg, Maija Wolf, Anne-Lise Borresen-Dale, Olli Kallioniemi
Genome Biology , 2011, DOI: 10.1186/gb-2011-12-1-r6
Abstract: We applied paired-end RNA-seq to identify 24 novel and 3 previously known fusion genes in breast cancer cells. Supported by an improved bioinformatic approach, we had a 95% success rate of validating gene fusions initially detected by RNA-seq. Fusion partner genes were found to contribute promoters (5' UTR), coding sequences and 3' UTRs. Most fusion genes were associated with copy number transitions and were particularly common in high-level DNA amplifications. This suggests that fusion events may contribute to the selective advantage provided by DNA amplifications and deletions. Some of the fusion partner genes, such as GSDMB in the TATDN1-GSDMB fusion and IKZF3 in the VAPB-IKZF3 fusion, were only detected as a fusion transcript, indicating activation of a dormant gene by the fusion event. A number of fusion gene partners have either been previously observed in oncogenic gene fusions, mostly in leukemias, or otherwise reported to be oncogenic. RNA interference-mediated knock-down of the VAPB-IKZF3 fusion gene indicated that it may be necessary for cancer cell growth and survival.In summary, using RNA-sequencing and improved bioinformatic stratification, we have discovered a number of novel fusion genes in breast cancer, and identified VAPB-IKZF3 as a potential fusion gene with importance for the growth and survival of breast cancer cells.Gene fusions are a well-known mechanism for oncogene activation in leukemias, lymphomas and sarcomas, with the BCR-ABL fusion gene in chronic myeloid leukemia as the prototype example [1,2]. The recent identification of recurrent ETS-family translocations in prostate cancer [3] and EML4-ALK in lung cancer [4] now suggests that fusion genes may play an important role also in the development of epithelial cancers. The reason why they were not previously detected was the lack of suitable techniques to identify balanced recurrent chromosomal aberrations in the often chaotic karyotypic profiles of solid tumors.Massively parallel RNA-seq
Gene expression profiles of primary colorectal carcinomas, liver metastases, and carcinomatoses
Kristine Kleivi, Guro E Lind, Chieu B Diep, Gunn I Meling, Lin T Brandal, Jahn M Nesland, Ola Myklebost, Torleiv O Rognum, Karl-Erik Giercksky, Rolf I Skotheim, Ragnhild A Lothe
Molecular Cancer , 2007, DOI: 10.1186/1476-4598-6-2
Abstract: Transcriptome profiles of colorectal cancer metastases independent of tumor site, as well as separate profiles associated with primary carcinomas, liver metastases, or peritoneal carcinomatoses, were assessed by use of Bayesian statistics. Gains of chromosome arm 5p are common in peritoneal carcinomatoses and several candidate genes (including PTGER4, SKP2, and ZNF622) mapping to this region were overexpressed in the tumors. Expression signatures stratified on TP53 mutation status were identified across all tumors regardless of stage. Furthermore, the gene expression levels for the in vivo tumors were compared with an in vitro model consisting of cell lines representing all three tumor stages established from one patient.By statistical analysis of gene expression data from primary colorectal carcinomas, liver metastases, and carcinomatoses, we are able to identify genetic patterns associated with the different stages of tumorigenesis.Colorectal cancer (CRC) is the second most common cause of cancer related deaths in developed countries, including Norway [1,2]. Despite the fact that metastases are the leading cause of colorectal cancer deaths, the majority of genetic studies of colorectal carcinogenesis have focused on changes found in primary carcinomas, and the knowledge about the underlying molecular changes in more advanced disease stages remain limited. To obtain insights to this process, identification of molecular key events that distinguish primary from metastatic tumors is important. DNA microarray technology has become powerful for whole-genome investigations [3]. Recently, several reports have shown that results obtained by this technology can distinguish among subgroups of the same cancer tissue [4-7] as well as among different cancer types [8]. Additionally, genetic profiles have been identified that predict patients' clinical outcome in cancers of the breast, lung, central nervous system, digestive system, and prostate [9-15]. Several studies has invest
Identifying In-Trans Process Associated Genes in Breast Cancer by Integrated Analysis of Copy Number and Expression Data
Miriam Ragle Aure, Israel Steinfeld, Lars Oliver Baumbusch, Knut Liest?l, Doron Lipson, Sandra Nyberg, Bj?rn Naume, Kristine Kleivi Sahlberg, Vessela N. Kristensen, Anne-Lise B?rresen-Dale, Ole Christian Lingj?rde, Zohar Yakhini
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0053014
Abstract: Genomic copy number alterations are common in cancer. Finding the genes causally implicated in oncogenesis is challenging because the gain or loss of a chromosomal region may affect a few key driver genes and many passengers. Integrative analyses have opened new vistas for addressing this issue. One approach is to identify genes with frequent copy number alterations and corresponding changes in expression. Several methods also analyse effects of transcriptional changes on known pathways. Here, we propose a method that analyses in-cis correlated genes for evidence of in-trans association to biological processes, with no bias towards processes of a particular type or function. The method aims to identify cis-regulated genes for which the expression correlation to other genes provides further evidence of a network-perturbing role in cancer. The proposed unsupervised approach involves a sequence of statistical tests to systematically narrow down the list of relevant genes, based on integrative analysis of copy number and gene expression data. A novel adjustment method handles confounding effects of co-occurring copy number aberrations, potentially a large source of false positives in such studies. Applying the method to whole-genome copy number and expression data from 100 primary breast carcinomas, 6373 genes were identified as commonly aberrant, 578 were highly in-cis correlated, and 56 were in addition associated in-trans to biological processes. Among these in-trans process associated and cis-correlated (iPAC) genes, 28% have previously been reported as breast cancer associated, and 64% as cancer associated. By combining statistical evidence from three separate subanalyses that focus respectively on copy number, gene expression and the combination of the two, the proposed method identifies several known and novel cancer driver candidates. Validation in an independent data set supports the conclusion that the method identifies genes implicated in cancer.
Origins and the Reasons of Monetary Crises in Georgia (1995-2016)  [PDF]
David Aslanishvili, Kristine Omadze
Modern Economy (ME) , 2016, DOI: 10.4236/me.2016.711119
Abstract: The article “Monetary Crises in Georgia (Authors: Doctor of Economy, David Aslanishvili and Doctor of Business Administration, Kristine Omadze) is the first attempt to overview the three main monetary crises in Georgian history since its independence and to study origins of the crises and evolution. The purpose of this article is to study the three monetary crises in Georgia itself and the errors in the Monetary Policy provided by The National Bank of Georgia and Georgian Government. It is crucial for stable economic development to have corrected Monetary Policy and to avoid mistakes similar to the mentioned in this article. At the same time, the article pays attention to importance of coordination providing Monetary Policy between the National Bank of Georgia and the Ministry of Finance. In our opinion only such coordination is the best solution for crisis prevention. Our research aims to determine the relevance and regularity of Georgian Lari (GEL) exchange rate and monetary policies conducted by the National Bank of Georgia.
miRNA-mRNA Integrated Analysis Reveals Roles for miRNAs in Primary Breast Tumors
Espen Enerly,Israel Steinfeld,Kristine Kleivi,Suvi-Katri Leivonen,Miriam R. Aure,Hege G. Russnes,Jo Anders R?nneberg,Hilde Johnsen,Roy Navon,Einar R?dland,Rami M?kel?,Bj?rn Naume,Merja Per?l?,Olli Kallioniemi,Vessela N. Kristensen,Zohar Yakhini,Anne-Lise B?rresen-Dale
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0016915
Abstract: Few studies have performed expression profiling of both miRNA and mRNA from the same primary breast carcinomas. In this study we present and analyze data derived from expression profiling of 799 miRNAs in 101 primary human breast tumors, along with genome-wide mRNA profiles and extensive clinical information.
Glomalin and Soil Aggregation under Six Management Systems in the Northern Great Plains, USA  [PDF]
Kristine A. Nichols, James Millar
Open Journal of Soil Science (OJSS) , 2013, DOI: 10.4236/ojss.2013.38043
Abstract:

The soil environment is linked to aboveground management including plant species composition, grazing intensity, levels of soil disturbance, residue management, and the length of time of a living plant is growing. Soil samples were collected under rangeland [native grass, rotational grazing (NGRG); tame grass, heavy grazing (TGRG); and tame grass, rotational grazing (TGHG)] and cropland [conventional till (CT); CT plus manure (CTM); and long term no till (NT)] systems. The rangeland systems were hypothesized to have higher glomalin content [measured as Bradford-reactive soil protein (BRSP)] and water stable aggregation (WSA) than the cropland systems. In addition, within both rangeland and cropland systems, BRSP and WSA were expected to decline with increased disturbance due to grazing or tillage and going from native to introduced plant species. Differences were detected for BRSP with NGRG and CTM having the highest values in range and cropland systems, respectively. However, the CTM system had higher BRSP values than one or both of the tame grass systems while the CT and NT systems had similar values. Correlation analysis showed strong relationships between all of the BRSP values and WSA.

Focusing Anti-Corruption Efforts More Effectively: An Empirical Look at Offender Motivation—Positive, Classical, Structural and Ethical Approaches  [PDF]
Jay S. Albanese, Kristine Artello
Advances in Applied Sociology (AASoci) , 2018, DOI: 10.4236/aasoci.2018.86028
Abstract: The level of public corruption cases remains high. Interviews with 72 former investigators, prosecutors, community stakeholders and individuals with first-hand experience in corrupt activities, together with analysis of court documents, offer insight into the motivations behind the corrupt conduct in hundreds of known corruption cases. Corrupt motivations are classified into four categories: positive, classical, structural, and ethical. Empirical examples from interviews and court cases are used to show how the identified causes and correlates of corruption can be grouped and use to develop more effective anti-corruption prevention strategies. Recommendations are offered to reduce the extent of corruption by applying the principles of positive, classical, structural, and ethical explanations of corruption to reduce opportunities for corruption and improve the integrity levels of those in public service.
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