130 results on '"Toth, Reka"'
Search Results
102. Ras-pathway mutation patterns define epigenetic subclasses in juvenile myelomonocytic leukemia
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Lipka, Daniel, primary, Witte, Tania, additional, Toth, Reka, additional, Yang, Jing, additional, Wiesenfarth, Manuel, additional, Nöllke, Peter, additional, Fischer, Alexandra, additional, Brocks, David, additional, Gu, Zuguang, additional, Park, Jeongbin, additional, Strahm, Brigitte, additional, Wlodarski, Marcin, additional, Yoshimi, Ayami, additional, Claus, Rainer, additional, Lübbert, Michael, additional, Busch, Hauke, additional, Börries, Melanie, additional, Catalá, Albert, additional, De Moerloose, Barbara, additional, Dworzak, Michael, additional, Hasle, Henrik, additional, Locatelli, Franco, additional, Masetti, Riccardo, additional, Smith, Owen, additional, Schmugge, Markus, additional, Stary, Jan, additional, Ussowicz, Marek, additional, van den Heuvel-Eibrink, Marry, additional, Assenov, Yassen, additional, Schlesner, Matthias, additional, Niemeyer, Charlotte, additional, Flotho, Christian, additional, and Plass, Christoph, additional
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- 2017
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103. Protein Quality Control and the Amyotrophic Lateral Sclerosis/Frontotemporal Dementia Continuum
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Shahheydari, Hamideh, primary, Ragagnin, Audrey, additional, Walker, Adam K., additional, Toth, Reka P., additional, Vidal, Marta, additional, Jagaraj, Cyril J., additional, Perri, Emma R., additional, Konopka, Anna, additional, Sultana, Jessica M., additional, and Atkin, Julie D., additional
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- 2017
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104. Metabolomics and transcriptomics identify pathway differences between visceral and subcutaneous adipose tissue in colorectal cancer patients: the ColoCare study
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Liesenfeld, David B, Grapov, Dmitry, Fahrmann, Johannes F, Salou, Mariam, Scherer, Dominique, Toth, Reka, Habermann, Nina, Böhm, Jürgen, Schrotz-King, Petra, Gigic, Biljana, Schneider, Martin, Ulrich, Alexis, Herpel, Esther, Schirmacher, Peter, Fiehn, Oliver, Lampe, Johanna W, and Ulrich, Cornelia M
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Male ,obesity ,Panniculitis ,Paraneoplastic Syndromes ,Subcutaneous Fat ,colorectal cancer ,Intra-Abdominal Fat ,Medical and Health Sciences ,Cohort Studies ,Engineering ,Clinical Research ,Humans ,Metabolomics ,2.1 Biological and endogenous factors ,Abdominal ,Prospective Studies ,Aetiology ,Metabolic and endocrine ,Neoplasm Staging ,Oligonucleotide Array Sequence Analysis ,Aged ,visceral adiposity ,Nutrition ,Cancer ,Neoplastic ,Nutrition & Dietetics ,Gene Expression Profiling ,Carcinoma ,Middle Aged ,Lipid Metabolism ,adipose tissue ,Colo-Rectal Cancer ,Gene Expression Regulation ,inflammation ,Female ,Colorectal Neoplasms ,Digestive Diseases ,Biomarkers - Abstract
BackgroundMetabolic and transcriptomic differences between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) compartments, particularly in the context of obesity, may play a role in colorectal carcinogenesis. We investigated the differential functions of their metabolic compositions.ObjectivesBiochemical differences between adipose tissues (VAT compared with SAT) in patients with colorectal carcinoma (CRC) were investigated by using mass spectrometry metabolomics and gene expression profiling. Metabolite compositions were compared between VAT, SAT, and serum metabolites. The relation between patients' tumor stage and metabolic profiles was assessed.DesignPresurgery blood and paired VAT and SAT samples during tumor surgery were obtained from 59 CRC patients (tumor stages I-IV) of the ColoCare cohort. Gas chromatography time-of-flight mass spectrometry and liquid chromatography quadrupole time-of-flight mass spectrometry were used to measure 1065 metabolites in adipose tissue (333 identified compounds) and 1810 metabolites in serum (467 identified compounds). Adipose tissue gene expression was measured by using Illumina's HumanHT-12 Expression BeadChips.ResultsCompared with SAT, VAT displayed elevated markers of inflammatory lipid metabolism, free arachidonic acid, phospholipases (PLA2G10), and prostaglandin synthesis-related enzymes (PTGD/PTGS2S). Plasmalogen concentrations were lower in VAT than in SAT, which was supported by lower gene expression of FAR1, the rate-limiting enzyme for ether-lipid synthesis in VAT. Serum sphingomyelin concentrations were inversely correlated (P = 0.0001) with SAT adipose triglycerides. Logistic regression identified lipids in patients' adipose tissues, which were associated with CRC tumor stage.ConclusionsAs one of the first studies, we comprehensively assessed differences in metabolic, lipidomic, and transcriptomic profiles between paired human VAT and SAT and their association with CRC tumor stage. We identified markers of inflammation in VAT, which supports prior evidence regarding the role of visceral adiposity and cancer.
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- 2015
105. Aspirin Reduces Plasma Concentrations of the Oncometabolite 2-Hydroxyglutarate: Results of a Randomized, Double-Blind, Crossover Trial
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Liesenfeld, David B., primary, Botma, Akke, additional, Habermann, Nina, additional, Toth, Reka, additional, Weigel, Christoph, additional, Popanda, Odilia, additional, Klika, Karel D., additional, Potter, John D., additional, Lampe, Johanna W., additional, and Ulrich, Cornelia M., additional
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- 2016
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106. Associations Between Dietary Patterns and Longitudinal Quality of Life Changes in Colorectal Cancer Patients: The ColoCare Study.
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Gigic, Biljana, Boeing, Heiner, Toth, Reka, Böhm, Jürgen, Habermann, Nina, Scherer, Dominique, Schrotz-King, Petra, Abbenhardt-Martin, Clare, Skender, Stephanie, Brenner, Hermann, Chang-Claude, Jenny, Hoffmeister, Michael, Syrjala, Karen, Jacobsen, Paul B., Schneider, Martin, Ulrich, Alexis, and Ulrich, Cornelia M.
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FOOD habits ,COLON tumors ,CONFIDENCE intervals ,CONSTIPATION ,DIARRHEA ,FACTOR analysis ,FRUIT ,LONGITUDINAL method ,QUALITY of life ,QUESTIONNAIRES ,RECTUM tumors ,REGRESSION analysis ,RESEARCH ,TIME ,MATHEMATICAL variables ,VEGETABLES ,SAMPLE size (Statistics) ,ODDS ratio ,WESTERN diet - Abstract
Quality of life (QoL) is an important clinical outcome in cancer patients. We investigated associations between dietary patterns and QoL changes in colorectal cancer (CRC) patients. The study included 192 CRC patients with available EORTC QLQ-C30 data before and 12 months post-surgery and food frequency questionnaire data at 12 months post-surgery. Principal component analysis was used to identify dietary patterns. Multivariate regression models assessed associations between dietary patterns and QoL changes over time. We identified four major dietary patterns: “Western” dietary pattern characterized by high consumption of potatoes, red and processed meat, poultry, and cakes, “fruit&vegetable” pattern: high intake of vegetables, fruits, vegetable oils, and soy products, “bread&butter” pattern: high intake of bread, butter and margarine, and “high-carb” pattern: high consumption of pasta, grains, nonalcoholic beverages, sauces and condiments. Patients following a “Western” diet had lower chances to improve in physical functioning (OR = 0.45 [0.21–0.99]), constipation (OR = 0.30 [0.13–0.72]) and diarrhea (OR: 0.44 [0.20–0.98]) over time. Patients following a “fruit&vegetable” diet showed improving diarrhea scores (OR: 2.52 [1.21–5.34]. A “Western” dietary pattern after surgery is inversely associated with QoL in CRC patients, whereas a diet rich in fruits and vegetables may be beneficial for patients' QoL over time. [ABSTRACT FROM PUBLISHER]
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- 2018
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107. Smoking is associated with hypermethylation of the APC 1A promoter in colorectal cancer: the ColoCare Study.
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Barrow, Timothy M, Klett, Hagen, Toth, Reka, Böhm, Jürgen, Gigic, Biljana, Habermann, Nina, Scherer, Dominique, Schrotz‐King, Petra, Skender, Stephanie, Abbenhardt‐Martin, Clare, Zielske, Lin, Schneider, Martin, Ulrich, Alexis, Schirmacher, Peter, Herpel, Esther, Brenner, Hermann, Busch, Hauke, Boerries, Melanie, Ulrich, Cornelia M, and Michels, Karin B
- Abstract
Smoking tobacco is a known risk factor for the development of colorectal cancer and for mortality associated with the disease. Smoking has been reported to be associated with changes in DNA methylation in blood and in lung tumour tissues, although there has been scant investigation of how epigenetic factors may be implicated in the increased risk of developing colorectal cancer. To identify epigenetic changes associated with smoking behaviours, we performed epigenome-wide analysis of DNA methylation in colorectal tumours from 36 never-smokers, 47 former smokers, and 13 active smokers, and in adjacent mucosa from 49 never-smokers, 64 former smokers, and 18 active smokers. Our analyses identified 15 CpG sites within the APC 1A promoter that were significantly hypermethylated and 14 CpG loci within the NFATC1 gene body that were significantly hypomethylated ( pLIS < 1 × 10
−5 ) in the tumours of active smokers. The APC 1A promoter was hypermethylated in 7 of 36 tumours from never-smokers (19%), 12 of 47 tumours from former smokers (26%), and 8 of 13 tumours from active smokers (62%). Promoter hypermethylation was positively associated with duration of smoking (Spearman rank correlation, ρ = 0.26, p = 0.03) and was confined to tumours, with hypermethylation never being observed in adjacent mucosa. Further analysis of adjacent mucosa revealed significant hypomethylation of four loci associated with the TNXB gene in tissue from active smokers. Our findings provide exploratory evidence for hypermethylation of the key tumour suppressor gene APC being implicated in smoking-associated colorectal carcinogenesis. Further work is required to establish the validity of our observations in independent cohorts. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]- Published
- 2017
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108. Abstract 4612: Genetic variants in epigenetic pathways and risk of multiple cancer types in the GAME-ON consortium
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Scherer, Dominique, primary, Toth, Reka, additional, Kelemen, Linda, additional, Risch, Angela, additional, Hazra, Aditi, additional, Issa, Jean Pierre, additional, Moreno, Victor, additional, Eeles, Rosalind A., additional, Quackenbush, John, additional, Goode, Ellen L., additional, Ogino, Shuji, additional, Hung, Rayjean, additional, and Ulrich, Cornelia M., additional
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- 2015
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109. Abstract 4590: Polymorphisms in cell-cycle related genes modify the effect of NSAIDs on the risk of colorectal cancer
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Toth, Reka, primary, Balavarca, Yesilda, additional, Scherer, Dominique, additional, Habermann, Nina, additional, Buck, Katharina, additional, Botma, Akke, additional, Kap, Elisabeth J., additional, Benner, Axel, additional, Ulrich, Alexis, additional, Hoffmeister, Michael, additional, Brenner, Hermann, additional, Burwinkel, Barbara, additional, Chang-Claude, Jenny, additional, and Ulrich, Cornelia M., additional
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- 2015
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110. Abstract 4585: Folate-mediated one-carbon metabolism polymorphisms associated with risk and survival of colorectal cancer
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Botma, Akke, primary, Buck, Katharina, additional, Balavarca, Yesilda, additional, Scherer, Dominique, additional, Habermann, Nina, additional, Toth, Reka, additional, Jansen, Lina, additional, Hoffmeister, Michael, additional, Brenner, Hermann, additional, Kap, Elisabeth J., additional, Seibold, Petra, additional, Benner, Axel, additional, Ulrich, Alexis, additional, Burwinkel, Barbara, additional, Chang-Claude, Jenny, additional, and Ulrich, Cornelia M., additional
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- 2015
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111. Changes in urinary metabolic profiles of colorectal cancer patients enrolled in a prospective cohort study (ColoCare)
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Liesenfeld, David B., primary, Habermann, Nina, additional, Toth, Reka, additional, Owen, Robert W., additional, Frei, Eva, additional, Böhm, Jürgen, additional, Schrotz-King, Petra, additional, Klika, Karel D., additional, and Ulrich, Cornelia M., additional
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- 2014
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112. USING DEA TO EVALUATE EFFICIENCY OF HIGHER EDUCATION
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Toth, Reka
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Productivity Analysis ,production efficiency ,Agricultural and Food Policy ,higher education ,Agribusiness ,Teaching/Communication/Extension/Profession ,data envelopment analysis ,sensitivity ,Tobit regression - Abstract
The aim of the higher education reform process both in Hungary and in the European countries is establishing a competitive, qualitative higher education with efficiently operating institutions. The question of efficiency needs increased attention not only because of the decline of the state support but also the rapid raise of the student mass. In the education system it’s not easy to measure the output of the services. The situation is more complicated if an organisation or a sector has multiple inputs and outputs. In this case a possible method of determining efficiency is Data Envelopment Analysis. In my paper I’d like to introduce this method and use it to compare the efficiency of higher education systems. Furthermore I am examining whether their efficiency is influenced by the extent of the contribution of the state and the private sector or socio-economic factors like GDP per capita and education level of parents.
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- 2009
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113. Genetic Variants in Epigenetic Pathways and Risks of Multiple Cancers in the GAME-ON Consortium.
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Toth, Reka, Scherer, Dominique, Kelemen, Linda E., Risch, Angela, Hazra, Aditi, Balavarca, Yesilda, Issa, Jean-Pierre J., Moreno, Victor, Eeles, Rosalind A., Shuji Ogino, Xifeng Wu, Yuanqing Ye, Hung, Rayjean J., Goode, Ellen L., and Ulrich, Cornelia M.
- Abstract
Background: Epigenetic disturbances are crucial in cancer initiation, potentially with pleiotropic effects, and may be influenced by the genetic background. Methods: In a subsets (ASSET) meta-analytic approach, we investigated associations of genetic variants related to epigenetic mechanisms with risks of breast, lung, colorectal, ovarian and prostate carcinomas using 51,724 cases and 52,001 controls. False discovery rate-corrected P values (q values < 0.05) were considered statistically significant. Results: Among 162,887 imputed or genotyped variants in 555 candidate genes, SNPs in eight genes were associated with risk of more than one cancer type. For example, variants in BABAM1 were confirmed as a susceptibility locus for squamous cell lung, overall breast, estrogen receptor (ER)-negative breast, and overall prostate, and overall serous ovarian cancer; the most significant variant was rs4808076 [OR = 1.14; 95% confidence interval (CI) = 1.10-1.19; q = 6.87 × 10
-5 ]. DPF1 rs12611084 was inversely associated with ER-negative breast, endometrioid ovarian, and overall and aggressive prostate cancer risk (OR = 0.93; 95% CI = 0.91-0.96; q = 0.005). Variants in L3MBTL3 were associated with colorectal, overall breast, ER-negative breast, clear cell ovarian, and overall and aggressive prostate cancer risk (e.g., rs9388766: OR = 1.06; 95% CI = 1.03-1.08; q = 0.02). Variants in TET2 were significantly associated with overall breast, overall prostate, overall ovarian, and endometrioid ovarian cancer risk, with rs62331150 showing bidirectional effects. Analyses of subpathways did not reveal gene subsets that contributed disproportionately to susceptibility. Conclusions: Functional and correlative studies are now needed to elucidate the potential links between germline genotype, epigenetic function, and cancer etiology. Impact: This approach provides novel insight into possible pleiotropic effects of genes involved in epigenetic processes. [ABSTRACT FROM AUTHOR]- Published
- 2017
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114. Abstract 2186: Inflammation- and angiogenesis- related genes: Interaction with NSAID use, and serum inflammatory markers on colorectal cancer risk within the Women's Health Initiative
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Habermann, Nina, primary, Brown, Elissa, additional, Toth, Reka, additional, Scherer, Dominique, additional, Buck, Katharina, additional, Cheng, Ting-Yuan David, additional, Makar, Karen W., additional, Neuhouser, Marian L., additional, Zheng, Yingye, additional, Duggan, David J., additional, Beresford, Shirley A., additional, Wener, Mark, additional, Ochs-Balcom, Heather, additional, Toriola, Adetunji, additional, and Ulrich, Cornelia M., additional
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- 2014
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115. Abstract 2197: Interaction between genetic variants in one-carbon metabolism and folate biomarkers on colorectal cancer risk: The Women's Health Initiative observational cohort
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Cheng, Ting-Yuan D., primary, Makar, Karen W., additional, Neuhouser, Marian L., additional, Miller, Joshua W., additional, Song, Xiaoling, additional, Brown, Elissa C., additional, Beresford, Shirley A.A., additional, Zheng, Yingye, additional, Duggan, David J., additional, Poole, Elizabeth M., additional, Habermann, Nina, additional, Toth, Reka, additional, Bailey, Lynn B., additional, Caudill, Marie A., additional, and Ulrich, Cornelia M., additional
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- 2014
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116. DNA Methylation Characteristics of Primary Melanomas with Distinct Biological Behaviour
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Ecsedi, Szilvia, primary, Hernandez-Vargas, Hector, additional, Lima, Sheila C., additional, Vizkeleti, Laura, additional, Toth, Reka, additional, Lazar, Viktoria, additional, Koroknai, Viktoria, additional, Kiss, Timea, additional, Emri, Gabriella, additional, Herceg, Zdenko, additional, Adany, Roza, additional, and Balazs, Margit, additional
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- 2014
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117. Correction: Integrative Genomics Identifies Gene Signature Associated with Melanoma Ulceration
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Rakosy, Zsuzsa, primary, Ecsedi, Szilvia, additional, Toth, Reka, additional, Vizkeleti, Laura, additional, Herandez-Vargas, Hector, additional, Lazar, Viktoria, additional, Emri, Gabriella, additional, Szatmari, Istvan, additional, Herceg, Zdenko, additional, Adany, Roza, additional, and Balazs, Margit, additional
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- 2013
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118. Integrative Genomics Identifies Gene Signature Associated with Melanoma Ulceration
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Rakosy, Zsuzsa, primary, Ecsedi, Szilvia, additional, Toth, Reka, additional, Vizkeleti, Laura, additional, Herandez-Vargas, Hector, additional, Lazar, Viktoria, additional, Emri, Gabriella, additional, Szatmari, Istvan, additional, Herceg, Zdenko, additional, Adany, Roza, additional, and Balazs, Margit, additional
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- 2013
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119. Glutamate receptor metabotropic 7 is cis-regulated in the mouse brain and modulates alcohol drinking
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Vadasz, Csaba, primary, Saito, Mariko, additional, Gyetvai, Beatrix M., additional, Oros, Melinda, additional, Szakall, Istvan, additional, Kovacs, Krisztina M., additional, Prasad, Vidudala V.T.S., additional, and Toth, Reka, additional
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- 2007
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120. Genome-Wide Interaction Analyses between Genetic Variants and Alcohol Consumption and Smoking for Risk of Colorectal Cancer
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Gong, Jian, Hutter, Carolyn M., Newcomb, Polly A., Ulrich, Cornelia M., Bien, Stephanie A., Campbell, Peter T., Baron, John A., Berndt, Sonja I., Bezieau, Stephane, Brenner, Hermann, Casey, Graham, Chan, Andrew T., Chang-Claude, Jenny, Du, Mengmeng, Duggan, David, Figueiredo, Jane C., Gallinger, Steven, Giovannucci, Edward L., Haile, Robert W., Harrison, Tabitha A., Hayes, Richard B., Hoffmeister, Michael, Hopper, John L., Hudson, Thomas J., Jeon, Jihyoun, Jenkins, Mark A., Kocarnik, Jonathan, Küry, Sébastien, Le Marchand, Loic, Lin, Yi, Lindor, Noralane M., Nishihara, Reiko, Ogino, Shuji, Potter, John D., Rudolph, Anja, Schoen, Robert E., Schrotz-King, Petra, Seminara, Daniela, Slattery, Martha L., Thibodeau, Stephen N., Thornquist, Mark, Toth, Reka, Wallace, Robert, White, Emily, Jiao, Shuo, Lemire, Mathieu, Hsu, Li, and Peters, Ulrike
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Biology and Life Sciences ,Nutrition ,Diet ,Alcohol Consumption ,Medicine and Health Sciences ,Oncology ,Cancers and Neoplasms ,Colorectal Cancer ,Genetics ,Gene Expression ,Behavior ,Habits ,Smoking Habits ,Anatomy ,Digestive System ,Gastrointestinal Tract ,Colon ,Epidemiology ,Genetic Epidemiology ,Adenomas ,Computational Biology ,Genome Analysis ,Genome-Wide Association Studies ,Genomics ,Human Genetics - Abstract
Genome-wide association studies (GWAS) have identified many genetic susceptibility loci for colorectal cancer (CRC). However, variants in these loci explain only a small proportion of familial aggregation, and there are likely additional variants that are associated with CRC susceptibility. Genome-wide studies of gene-environment interactions may identify variants that are not detected in GWAS of marginal gene effects. To study this, we conducted a genome-wide analysis for interaction between genetic variants and alcohol consumption and cigarette smoking using data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Interactions were tested using logistic regression. We identified interaction between CRC risk and alcohol consumption and variants in the 9q22.32/HIATL1 (Pinteraction = 1.76×10−8; permuted p-value 3.51x10-8) region. Compared to non-/occasional drinking light to moderate alcohol consumption was associated with a lower risk of colorectal cancer among individuals with rs9409565 CT genotype (OR, 0.82 [95% CI, 0.74–0.91]; P = 2.1×10−4) and TT genotypes (OR,0.62 [95% CI, 0.51–0.75]; P = 1.3×10−6) but not associated among those with the CC genotype (p = 0.059). No genome-wide statistically significant interactions were observed for smoking. If replicated our suggestive finding of a genome-wide significant interaction between genetic variants and alcohol consumption might contribute to understanding colorectal cancer etiology and identifying subpopulations with differential susceptibility to the effect of alcohol on CRC risk.
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- 2016
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121. Genome-Wide Interaction Analyses between Genetic Variants and Alcohol Consumption and Smoking for Risk of Colorectal Cancer
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Hopper, John L., Seminara, Daniela, Toth, Reka, Campbell, Peter T., Hoffmeister, Michael, Harrison, Tabitha A., Potter, John D., Thibodeau, Stephen N., Küry, Sébastien, Hsu, Li, Giovannucci, Edward L., Berndt, Sonja I., Bien, Stephanie A., Newcomb, Polly A., Thornquist, Mark, Haile, Robert W., Jiao, Shuo, Lemire, Mathieu, Bezieau, Stephane, Gallinger, Steven, Jenkins, Mark A., White, Emily, Rudolph, Anja, Gong, Jian, Du, Mengmeng, Baron, John A., Peters, Ulrike, Schrotz-King, Petra, Jeon, Jihyoun, Hutter, Carolyn M., Schoen, Robert E., Ulrich, Cornelia M., Slattery, Martha L., Nishihara, Reiko, Ogino, Shuji, Duggan, David, Casey, Graham, Brenner, Hermann, Wallace, Robert, Lindor, Noralane M., Hayes, Richard B., Le Marchand, Loic, Lin, Yi, Figueiredo, Jane C., Chang-Claude, Jenny, Chan, Andrew T., Kocarnik, Jonathan, and Hudson, Thomas J.
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3. Good health - Abstract
Genome-wide association studies (GWAS) have identified many genetic susceptibility loci for colorectal cancer (CRC). However, variants in these loci explain only a small proportion of familial aggregation, and there are likely additional variants that are associated with CRC susceptibility. Genome-wide studies of gene-environment interactions may identify variants that are not detected in GWAS of marginal gene effects. To study this, we conducted a genome-wide analysis for interaction between genetic variants and alcohol consumption and cigarette smoking using data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Interactions were tested using logistic regression. We identified interaction between CRC risk and alcohol consumption and variants in the 9q22.32/HIATL1 (Pinteraction = 1.76×10−8; permuted p-value 3.51x10-8) region. Compared to non-/occasional drinking light to moderate alcohol consumption was associated with a lower risk of colorectal cancer among individuals with rs9409565 CT genotype (OR, 0.82 [95% CI, 0.74–0.91]; P = 2.1×10−4) and TT genotypes (OR,0.62 [95% CI, 0.51–0.75]; P = 1.3×10−6) but not associated among those with the CC genotype (p = 0.059). No genome-wide statistically significant interactions were observed for smoking. If replicated our suggestive finding of a genome-wide significant interaction between genetic variants and alcohol consumption might contribute to understanding colorectal cancer etiology and identifying subpopulations with differential susceptibility to the effect of alcohol on CRC risk.
122. Differential expression of tissue transglutaminase during in vivo apoptosis of thymocytes induced via distinct signalling pathways
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Szondy, Zsuzsa, Molnar, Peter, Nemes, Zoltán, Boyiadzis, Michael, Kedei, Noémi, Tóth, Réka, and Fésüs, László
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- 1997
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123. RAS-pathway mutation patterns define epigenetic subclasses in juvenile myelomonocytic leukemia
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Umut Kilik, Reka Toth, Rainer Claus, Tania Witte, Ayami Yoshimi, Christoph Plass, Peter Nöllke, Michael Dworzak, Melanie Boerries, Maximilian Schönung, Alexandra Fischer, Jing Yang, Zuguang Gu, Caroline Pabst, Daniel B. Lipka, Barbara De Moerloose, Charlotte M. Niemeyer, David Brocks, Jan Stary, Michael Lübbert, Jeongbin Park, Matthias Schlesner, Albert Català, Hauke Busch, Owen P. Smith, Christian Flotho, Marek Ussowicz, Franco Locatelli, Yassen Assenov, Manuel Wiesenfarth, Riccardo Masetti, Jens Langstein, Marry M. van den Heuvel-Eibrink, Swati Garg, Justyna A. Wierzbinska, Brigitte Strahm, Mark Hartmann, Henrik Hasle, Marcin W. Wlodarski, Markus Schmugge, Lipka, Daniel B., Witte, Tania, Toth, Reka, Yang, Jing, Wiesenfarth, Manuel, Nöllke, Peter, Fischer, Alexandra, Brocks, David, Gu, Zuguang, Park, Jeongbin, Strahm, Brigitte, Wlodarski, Marcin, Yoshimi, Ayami, Claus, Rainer, Lübbert, Michael, Busch, Hauke, Boerries, Melanie, Hartmann, Mark, Schönung, Maximilian, Kilik, Umut, Langstein, Jen, Wierzbinska, Justyna A., Pabst, Caroline, Garg, Swati, Catalá, Albert, De Moerloose, Barbara, Dworzak, Michael, Hasle, Henrik, Locatelli, Franco, Masetti, Riccardo, Schmugge, Marku, Smith, Owen, Stary, Jan, Ussowicz, Marek, Van Den Heuvel-Eibrink, Marry M., Assenov, Yassen, Schlesner, Matthia, Niemeyer, Charlotte, Flotho, Christian, and Plass, Christoph
- Subjects
Epigenomics ,0301 basic medicine ,Neuroblastoma RAS viral oncogene homolog ,Male ,Biopsy ,DNA Mutational Analysis ,General Physics and Astronomy ,CIS-REGULATORY ELEMENTS ,Protein Tyrosine Phosphatase, Non-Receptor Type 11 ,medicine.disease_cause ,juvenile myelomonocytic leukemia ,children ,DNA mutations ,Antineoplastic Agent ,0302 clinical medicine ,Medicine and Health Sciences ,DNA (Cytosine-5-)-Methyltransferases ,Prospective Studies ,Proto-Oncogene Proteins c-cbl ,Child ,lcsh:Science ,JMML ,Mutation ,Multidisciplinary ,Juvenile myelomonocytic leukemia ,Gene Expression Regulation, Leukemic ,ISLAND METHYLATOR PHENOTYPE ,Noonan Syndrome ,Chemistry (all) ,METHYLATION ,Hematopoietic Stem Cell Transplantation ,EPITHELIAL-CELLS ,Prognosis ,Chromatin ,Up-Regulation ,Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,030220 oncology & carcinogenesis ,Child, Preschool ,DNA methylation ,NERVE SHEATH TUMORS ,Female ,KRAS ,Human ,Signal Transduction ,DNA (Cytosine-5-)-Methyltransferase 1 ,Epigenomic ,Prognosi ,Science ,Antineoplastic Agents ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,DNA Mutational Analysi ,Proto-Oncogene Proteins p21(ras) ,03 medical and health sciences ,Physics and Astronomy (all) ,medicine ,MYELODYSPLASTIC SYNDROMES ,Journal Article ,Humans ,Epigenetics ,ddc:610 ,Biochemistry, Genetics and Molecular Biology (all) ,CHRONIC LYMPHOCYTIC-LEUKEMIA ,TRANSPLANTATION ,Biology and Life Sciences ,Infant ,General Chemistry ,DNA ,SOMATIC MUTATIONS ,DNA Methylation ,medicine.disease ,STEM-CELL ,PTPN11 ,Prospective Studie ,030104 developmental biology ,Leukemia, Myelomonocytic, Juvenile ,MOLECULAR CLASSIFICATION ,DNA (Cytosine-5-)-Methyltransferase ,Cancer research ,lcsh:Q - Abstract
Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative disorder of early childhood characterized by mutations activating RAS signaling. Established clinical and genetic markers fail to fully recapitulate the clinical and biological heterogeneity of this disease. Here we report DNA methylome analysis and mutation profiling of 167 JMML samples. We identify three JMML subgroups with unique molecular and clinical characteristics. The high methylation group (HM) is characterized by somatic PTPN11 mutations and poor clinical outcome. The low methylation group is enriched for somatic NRAS and CBL mutations, as well as for Noonan patients, and has a good prognosis. The intermediate methylation group (IM) shows enrichment for monosomy 7 and somatic KRAS mutations. Hypermethylation is associated with repressed chromatin, genes regulated by RAS signaling, frequent co-occurrence of RAS pathway mutations and upregulation of DNMT1 and DNMT3B, suggesting a link between activation of the DNA methylation machinery and mutational patterns in JMML., Juvenile myelomonocytic leukemia (JMML) is an aggressive disease with limited options for treatment. Here, the authors analyse the DNA methylome and mutational profile of JMML to define three subgroups with unique molecular and clinical characteristics.
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- 2017
124. consICA: an R package for robust reference-free deconvolution of multi-omics data.
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Chepeleva M, Kaoma T, Zinovyev A, Toth R, and Nazarov PV
- Abstract
Motivation: Deciphering molecular signals from omics data helps understanding cellular processes and disease progression. Effective algorithms for extracting these signals are essential, with a strong emphasis on robustness and reproducibility., Results: R/Bioconductor package consICA implements consensus independent component analysis (ICA)-a data-driven deconvolution method to decompose heterogeneous omics data and extract features suitable for patient stratification and multimodal data integration. The method separates biologically relevant molecular signals from technical effects and provides information about the cellular composition and biological processes. Build-in annotation, survival analysis, and report generation provide useful tools for the interpretation of extracted signals. The implementation of parallel computing in the package ensures efficient analysis using modern multicore systems. The package offers a reproducible and efficient data-driven solution for the analysis of complex molecular profiles, with significant implications for cancer research., Availability and Implementation: The package is implemented in R and available under MIT license at Bioconductor (https://bioconductor.org/packages/consICA) or at GitHub (https://github.com/biomod-lih/consICA)., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press.)
- Published
- 2024
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125. Discovery of active mouse, plant and fungal cytochrome P450s in endogenous proteomes and upon expression in planta.
- Author
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Font-Farre M, Brown D, Toth R, Mahadevan C, Brazier-Hicks M, Morimoto K, Kaschani F, Sinclair J, Dale R, Hall S, Morris M, Kaiser M, Wright AT, Burton J, and van der Hoorn RAL
- Subjects
- Animals, Mice, Ascomycota metabolism, Plant Proteins metabolism, Plant Proteins genetics, Cytochrome P-450 Enzyme System metabolism, Cytochrome P-450 Enzyme System genetics, Proteome metabolism, Fungal Proteins metabolism, Fungal Proteins genetics
- Abstract
Eukaryotes produce a large number of cytochrome P450s that mediate the synthesis and degradation of diverse endogenous and exogenous metabolites. Yet, most of these P450s are uncharacterized and global tools to study these challenging, membrane-resident enzymes remain to be exploited. Here, we applied activity profiling of plant, mouse and fungal P450s with chemical probes that become reactive when oxidized by P450 enzymes. Identification by mass spectrometry revealed labeling of a wide range of active P450s, including six plant P450s, 40 mouse P450s and 13 P450s of the fungal wheat pathogen Zymoseptoria tritici. We next used transient expression of GFP-tagged P450s by agroinfiltration to show ER-targeting and NADPH-dependent, activity-based labeling of plant, mouse and fungal P450s. Both global profiling and transient expression can be used to detect a broad range of active P450s to study e.g. their regulation and discover selective inhibitors., (© 2024. The Author(s).)
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- 2024
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126. Glioblastoma-instructed microglia transition to heterogeneous phenotypic states with phagocytic and dendritic cell-like features in patient tumors and patient-derived orthotopic xenografts.
- Author
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Yabo YA, Moreno-Sanchez PM, Pires-Afonso Y, Kaoma T, Nosirov B, Scafidi A, Ermini L, Lipsa A, Oudin A, Kyriakis D, Grzyb K, Poovathingal SK, Poli A, Muller A, Toth R, Klink B, Berchem G, Berthold C, Hertel F, Mittelbronn M, Heiland DH, Skupin A, Nazarov PV, Niclou SP, Michelucci A, and Golebiewska A
- Subjects
- Mice, Animals, Humans, Microglia metabolism, Ecosystem, Heterografts, Phenotype, Disease Models, Animal, Dendritic Cells metabolism, Tumor Microenvironment genetics, Glioblastoma genetics, Glioblastoma metabolism, Brain Neoplasms genetics, Brain Neoplasms metabolism
- Abstract
Background: A major contributing factor to glioblastoma (GBM) development and progression is its ability to evade the immune system by creating an immune-suppressive environment, where GBM-associated myeloid cells, including resident microglia and peripheral monocyte-derived macrophages, play critical pro-tumoral roles. However, it is unclear whether recruited myeloid cells are phenotypically and functionally identical in GBM patients and whether this heterogeneity is recapitulated in patient-derived orthotopic xenografts (PDOXs). A thorough understanding of the GBM ecosystem and its recapitulation in preclinical models is currently missing, leading to inaccurate results and failures of clinical trials., Methods: Here, we report systematic characterization of the tumor microenvironment (TME) in GBM PDOXs and patient tumors at the single-cell and spatial levels. We applied single-cell RNA sequencing, spatial transcriptomics, multicolor flow cytometry, immunohistochemistry, and functional studies to examine the heterogeneous TME instructed by GBM cells. GBM PDOXs representing different tumor phenotypes were compared to glioma mouse GL261 syngeneic model and patient tumors., Results: We show that GBM tumor cells reciprocally interact with host cells to create a GBM patient-specific TME in PDOXs. We detected the most prominent transcriptomic adaptations in myeloid cells, with brain-resident microglia representing the main population in the cellular tumor, while peripheral-derived myeloid cells infiltrated the brain at sites of blood-brain barrier disruption. More specifically, we show that GBM-educated microglia undergo transition to diverse phenotypic states across distinct GBM landscapes and tumor niches. GBM-educated microglia subsets display phagocytic and dendritic cell-like gene expression programs. Additionally, we found novel microglial states expressing cell cycle programs, astrocytic or endothelial markers. Lastly, we show that temozolomide treatment leads to transcriptomic plasticity and altered crosstalk between GBM tumor cells and adjacent TME components., Conclusions: Our data provide novel insights into the phenotypic adaptation of the heterogeneous TME instructed by GBM tumors. We show the key role of microglial phenotypic states in supporting GBM tumor growth and response to treatment. Our data place PDOXs as relevant models to assess the functionality of the TME and changes in the GBM ecosystem upon treatment., (© 2024. The Author(s).)
- Published
- 2024
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127. Glioblastoma-instructed microglia transition to heterogeneous phenotypic states with phagocytic and dendritic cell-like features in patient tumors and patient-derived orthotopic xenografts.
- Author
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Yabo YA, Moreno-Sanchez PM, Pires-Afonso Y, Kaoma T, Nosirov B, Scafidi A, Ermini L, Lipsa A, Oudin A, Kyriakis D, Grzyb K, Poovathingal SK, Poli A, Muller A, Toth R, Klink B, Berchem G, Berthold C, Hertel F, Mittelbronn M, Heiland DH, Skupin A, Nazarov PV, Niclou SP, Michelucci A, and Golebiewska A
- Abstract
Background: A major contributing factor to glioblastoma (GBM) development and progression is its ability to evade the immune system by creating an immune-suppressive environment, where GBM-associated myeloid cells, including resident microglia and peripheral monocyte-derived macrophages, play critical pro-tumoral roles. However, it is unclear whether recruited myeloid cells are phenotypically and functionally identical in GBM patients and whether this heterogeneity is recapitulated in patient-derived orthotopic xenografts (PDOXs). A thorough understanding of the GBM ecosystem and its recapitulation in preclinical models is currently missing, leading to inaccurate results and failures of clinical trials., Methods: Here, we report systematic characterization of the tumor microenvironment (TME) in GBM PDOXs and patient tumors at the single-cell and spatial levels. We applied single-cell RNA-sequencing, spatial transcriptomics, multicolor flow cytometry, immunohistochemistry and functional studies to examine the heterogeneous TME instructed by GBM cells. GBM PDOXs representing different tumor phenotypes were compared to glioma mouse GL261 syngeneic model and patient tumors., Results: We show that GBM tumor cells reciprocally interact with host cells to create a GBM patient-specific TME in PDOXs. We detected the most prominent transcriptomic adaptations in myeloid cells, with brain-resident microglia representing the main population in the cellular tumor, while peripheral-derived myeloid cells infiltrated the brain at sites of blood-brain barrier disruption. More specifically, we show that GBM-educated microglia undergo transition to diverse phenotypic states across distinct GBM landscapes and tumor niches. GBM-educated microglia subsets display phagocytic and dendritic cell-like gene expression programs. Additionally, we found novel microglial states expressing cell cycle programs, astrocytic or endothelial markers. Lastly, we show that temozolomide treatment leads to transcriptomic plasticity and altered crosstalk between GBM tumor cells and adjacent TME components., Conclusions: Our data provide novel insights into the phenotypic adaptation of the heterogeneous TME instructed by GBM tumors. We show the key role of microglial phenotypic states in supporting GBM tumor growth and response to treatment. Our data place PDOXs as relevant models to assess the functionality of the TME and changes in the GBM ecosystem upon treatment., Competing Interests: Competing interests The authors declare that they have no competing interests.
- Published
- 2023
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128. Translocation t(6;7) in AML-M4 cell line GDM-1 results in MNX1 activation through enhancer-hijacking.
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Weichenhan D, Riedel A, Meinen C, Basic A, Toth R, Bähr M, Lutsik P, Hey J, Sollier E, Toprak UH, Kelekçi S, Lin YY, Hakobyan M, Touzart A, Goyal A, Wierzbinska JA, Schlesner M, Westermann F, Lipka DB, and Plass C
- Subjects
- Humans, Translocation, Genetic, Cell Line, Transcription Factors genetics, Homeodomain Proteins genetics, Leukemia, Myelomonocytic, Acute, Leukemia, Myeloid, Acute genetics
- Published
- 2023
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129. Methrix: an R/Bioconductor package for systematic aggregation and analysis of bisulfite sequencing data.
- Author
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Mayakonda A, Schönung M, Hey J, Batra RN, Feuerstein-Akgoz C, Köhler K, Lipka DB, Sotillo R, Plass C, Lutsik P, and Toth R
- Abstract
Motivation: Whole-genome bisulfite sequencing (WGBS) measures DNA methylation at base pair resolution resulting in large bedGraph like coverage files. Current options for processing such files are hindered by discrepancies in file format specification, speed, and memory requirements., Results: We developed methrix, an R package, which provides a toolset for systematic analysis of large datasets. Core functionality of the package includes a comprehensive bedGraph or similar tab-separated text file reader-which summarizes methylation calls based on annotated reference indices, infers and collapses strands and handles uncovered reference CpG sites while facilitating a flexible input file format specification. Additional optimized functions for quality control filtering, subsetting and visualization allow user-friendly and effective processing of WGBS results. Easy integration with tools for differentially methylated region (DMR) calling and annotation further eases the analysis of genome-wide methylation data. Overall, methrix enriches established WGBS workflows by bringing together computational efficiency and versatile functionality., Availability and Implementation: Methrix is implemented as an R package, made available under MIT license at https://github.com/CompEpigen/methrix and can be installed from the Bioconductor repository., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2021
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130. Prognostic relevance of the expressions of CAV1 and TES genes on 7q31 in melanoma.
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Vizkeleti L, Ecsedi S, Rakosy Z, Begany A, Emri G, Toth R, Orosz A, Szollosi AG, Mehes G, Adany R, and Balazs M
- Subjects
- Adult, Cell Line, Tumor, Female, Humans, In Situ Hybridization, Fluorescence, Male, Melanoma genetics, Middle Aged, Neoplasm Metastasis, Prognosis, RNA, Messenger genetics, RNA-Binding Proteins, Reverse Transcriptase Polymerase Chain Reaction, Caveolin 1 genetics, Chromosomes, Human, Pair 7, Cytoskeletal Proteins genetics, LIM Domain Proteins genetics, Melanoma pathology
- Abstract
The 7q31 locus contains several genes affected in cancer progression. Although evidences exist regarding its impact on tumorigenesis, the role of genetic alterations and the expressions of locus-related genes are still controversial. Our study aimed to define the 7q31 copy number alterations in primary melanomas, primary-metastatic tumor pairs and cell lines. Data were correlated with clinical-pathological parameters. Genetic data show that 7q31 copy number distribution was heterogeneous in both primary and metastatic tumors. Extra copies were highly accompanied by chromosome 7 polisomy, and significantly increased in primary lesions with poor prognosis. Additionally, we determined the mRNA and protein levels of the locus-related CAV1 and TES genes. TES mRNA level was associated with metastatic location. CAV1 mRNA and protein levels were significantly higher in thicker tumors, however, lack of protein was also observed in a subpopulation of thin lesions. Expressions of CAV1 and TES were not associated with 7q31 alterations. In conclusion, 7q31 amplification can predict unfavorable outcome. Alterations of TES mRNA level may predict the location of metastasis. CAV1 possibly affect the cancer cell invasion.
- Published
- 2012
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