bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4996: Genome-wide DNA methylation profiles in hepatocellular carcinoma
Authors: Shen Jing , Wang Shuang , Zhang Yujing , Kappil Maya , Wu Hui-Chen , Kibrya Muhammad G. , Wang Qiao , Jasmine Farzana , Ahsan Habib , Lee Po-Huang , Yu Ming-Whei , Chen Chien-Jen , Santella Regina M. 
Published: August 2012

Abstract
Alterations in DNA methylation frequently occur in hepatocellular cancer (HCC). We have previously demonstrated that hypermethylation in candidate genes can be detected in plasma DNA prior to HCC diagnosis. To identify with a genome-wide approach additional genes hypermethylated in HCC that could be used for more accurate analysis of plasma DNA for early diagnosis, we analyzed tumor and adjacent non-tumor tissues from 62 Taiwanese HCC cases using Illumina methylation arrays that screen 26,486 autosomal CpG sites. After Bonferroni adjustment, a total of 2,324 CpG sites significantly differed in methylation level, with 684 CpG sites significantly hypermethylated and 1,640 hypomethylated in tumor compared to non-tumor tissues. Array data were validated with pyrosequencing in a subset of 5 of these genes; correlation coefficients ranged from 0.92 to 0.97. Analysis of plasma DNA from 38 cases demonstrated that 37% to 63% of cases had detectable hypermethylated DNA (≥5% methylation) for these 5 genes individually. At least one of these genes was hypermethylated in 87% of cases, suggesting that measurement of DNA methylation in plasma samples is feasible. The panel of methylated genes indentified in the current study will be further tested in large cohort of prospectively collected samples to determine their utility as early biomarkers of hepatocellular carcinoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4996. doi:1538-7445.AM2012-4996
Abstract 4999: Genome-wide methylation array of human prostate tissues using illumina infunium 450K bead chip reveals distinct DNA methylation signatures with potential as clinical predictors
Authors: Kwabi-Addo Bernard , Wang Songping , Lee Norman H. , Ittmann Michael , Suer Funda , Devaney Joseph 
Published: August 2012

Abstract
Prostate cancer (PCa) harbors a myriad of aberrant genomic and epigenetic alterations. Epigenetic inactivation of genes in PCa is largely based on transcriptional silencing by aberrant CpG methylation of CpG rich promoter regions. Candidate gene-based studies have identified a handful of aberrant CpG DNA methylation events in PCa. To better understand the role of aberrant epigenetic alterations and identify biological pathways likely to be affected by methylation mediated alterations in gene expression in PCa, we have examined the methylation status of 450,000 (450K) cytosine microarray (illumina). The 450K microarray includes CpG islands/shores/shelves/open sea, non-coding RNA and sites surrounding the transcription start sites for coding genes, but also for the corresponding gene bodies and the 3′-UTR. We demonstrate that the 450k DNA methylation array can significantly detect CpG methylation changes in radical prostatectomy prostate tissue samples. Cluster analysis revealed distinct DNA methylation profiles for prostate cancer tissues in comparison with non-malignant tissues. A total of 225 CpG loci (p &gt; 0.00049) showed differential methylation in the cancer tissues in comparison with non-malignant tissues. Each of the 225 CpG locus was validated in silico using an independent, publicly available methylome dataset from the Cancer Genome Atlas. The majority of these loci were informative particularly in the prostate cancer. Overall, cluster analysis showed gene set enriched in pathways including transcriptional modifications, apoptosis/autophagy, chromatin assembly, growth factor signaling, cell cycle regulation and oxidative-redox reaction. This study shows that CpG locus methylation arrays could reveal important biological differences in the epigenome between prostate cancer and non-malignant tissues and provide potential markers for disease detection and/or progression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4999. doi:1538-7445.AM2012-4999
Abstract 500: DMP1 activates osteolytic cycle in a tumor environment
Authors: Eapen Asha S. , George Anne 
Published: August 2012

Abstract
Bone metastasis is one of the skeletal malignancies that could be caused by breast cancer. Dentin matrix protein 1 (DMP1) is an acidic noncollagenous protein localized specifically in the mineralized matrix of bone and dentin. It is a multifunctional protein, involved in gene regulation (within the cell) and HAP nucleation (in the ECM). DMP1 is endocytosed by preosteoblasts, triggering the calcium dependent and calcium independent signaling pathways resulting in a series of downstream events leading to osteoblast differentiation. These signaling events facilitate the activation of a calcium dependent stress-induced p38 MAP kinase and a calcium independent integrin mediated ERK1/2 MAP kinase pathway resulting in the expression of downstream target genes such as Runx2 and osteocalcin. Results from this study have shown that the osteoblast cells upon differentiation secrete receptor activator of nuclear factor kappa B ligand (RANKL) that stimulates the differentiation of precursor monocytes to osteoclasts. The study also focuses on identifying the role of DMP1 in breast cancer cells that could enhance osteoclast formation thereby accelerating bone resportion. Thus, the study reveals a new mechanism by which DMP1 can activate the vicious cycle leading to the aggressive growth and behavior of the cancer cells. To address the mechanism by which DMP1 might contribute to the osteolytic process, DMP1 was overexpressed in the metastatic cancer cell line MDA MB231. Upregulation of markers like Runx2, MMP2, MMP9, RANKL, OPN, BSP, VEGF and the activation of Smad2/3 and MAP kinase pathways (p38 and ERK1/2 pathways) were observed in overexpressed cells. Results from this study have shown that DMP1 secreted by the breast cancer cells into the extracellular environment could stimulate the differentiation of osteoblasts, leading to the secretion of factors that signal monocytes to differentiate to osteoclast thus resulting in bone metastasis. Overall, the results obtained from this study identify a new role for DMP1 in the differentiation of breast cancer tumor cells that may be directly related to their metastatic potential. Supported by NIH DE 115657 and the Brodie Endowment Fund
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 500. doi:1538-7445.AM2012-500
Abstract 5004: CpG island methylator phenotype in bladder cancer
Authors: Chung Woonbok , Bondaruk Jolanta , Zhang Nianxiang , Jelinek Jaroslav , Estecio Marcos , Liang Shoudan , Czerniak Bogdan , Issa Jean-Pierre J. 
Published: August 2012

Abstract
DNA hypermethylation is a common epigenetic abnormality in cancer, and some cancers are characterized by the presence of intense hypermethylation at multiple loci, termed CpG island methylation phenotype (CIMP). CIMP has not been fully characterized in bladder cancer. In a pilot study, we examined the methylation status of 38 loci in a panel of 26 bladder cancer and identified 14 genes whose methylation was concordant, supporting the presence of CIMP. In an expanded series of 108 cancers, we found that a distinct subset displays concerted hypermethylation at a large number of genes, confirming the existence of CIMP in bladder cancer. Unsupervised hierarchical K-means clustering identified three distinct DNA methylation groups of bladder cancers, CIMP-N (negative), CIMP-L (low), and CIMP-H (high) representing 39%, 33% and 28% of cancer overall. Compared to CIMP-N cases, CIMP-H cases were more frequently current smokers (p&lt;0.05), had more H-RAS and K-RAS mutation (15% vs. 0 %, P&lt; 0.05), had less FGFR3 mutations (8% vs. 32 %, P&lt;0.05) and more RB1 loss (35% vs. 10%, P&lt;0.05). Genome wide analysis of 85 bladder cancers by MCAM (methylated CpG island amplification microarray) showed an average of 12.4 % of genes hypermethylated in CIMP-H, 6.5 % in CIMP-L and 4.4 % in CIMP-N (CIMP-N vs. CIMP-L, p=0.0006 and CIMP-L vs. CIMP-H, p&lt;0.0001). Affected genes were enriched for PcG targets, and gene ontology analysis showed clustering at Homeobox and voltage-gated cation channel based on gene expression of CIMP targets. Our study suggests that CIMP is an important molecular variable in bladder cancer heterogeneity.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5004. doi:1538-7445.AM2012-5004
Abstract 5005: Large-scale DNA methylation profiling in gastrointestinal stromal tumors (GIST) reveals epigenetic regulation of SPP1 as an independent prognostic factor
Authors: Haller Florian , Zhang Jitao David , Riazalhosseini Yasser , Ward Aoife , Balwierz Aleksandra , Korn Bernhard , Schaefer Inga-Marie , Cameron Silke , Ghadimi B. Michael , Agaimy Abbas , Fletcher Jonathan A. , Hoheisel Jörg , Wiemann Stefan , Sahin Özgür 
Published: August 2012

Abstract
Aims Gastrointestinal stromal tumors (GISTs) have distinct gene expression patterns according to anatomical localisation and genotype, with potential impact on biological aggressiveness. DNA methylation of CpG dinucleotides in the promoter region of genes is an important mechanism for regulation of gene expression. We performed a large-scale analysis of DNA methylation in GISTs to identify methylation patterns associated with clinico-pathological parameters and prognosis. Methods Seventy-five GISTs with either KIT or PDGFRA mutations were analysed for DNA methylation of 1.505 CpG sites in the promoter regions of 807 cancer-related genes using a large-scale approach (Cancer Methylation Panel I, Illumina). Epigenetic regulation of Secreted Phosphoprotein 1 (SPP1) expression was analysed at mRNA and protein levels in GIST882 and GIST48b cells after treatment with a demethylating agent. Impacts on tumorigenesis-related signalling pathways were analysed by Western Blot after stimulation of GIST cell lines with SPP1. Prognostic impact of SPP1 at methylation and protein levels were investigated in 75 and 121 GIST tumor samples, respectively, and compared to classical prognostic parameters tumor size, mitotic counts and tumor localisation. Results Principal component analysis revealed distinct DNA methylation patterns according to anatomical localisation, genotype and mitotic counts. Hypomethylation of a CpG dinucleotide 647 base pairs upstream of the transcription start site of SPP1 was significantly correlated to SPP1 mRNA and protein level, and also to tumor progression (p=0.003). In vitro analyses confirmed epigenetic regulation of SPP1 expression, and demonstrated potential impact on proliferation and invasion. High protein level of SPP1 was significantly correlated to shorter disease-free survival in univariate (p=2x10−7) and multivariate (p&lt;1x10−6) analyses. Conclusion The expression of SPP1 is regulated epigenetically in GISTs, and high expression of SPP1 is a novel and independent prognostic parameter in GISTs.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5005. doi:1538-7445.AM2012-5005
Abstract 5006: High-throughput TR-FRET cellular assays for interrogating histone H3 methylation
Authors: Bi Kun , Dudek Jeanne , Hermanson Spencer 
Published: August 2012

Abstract
Post-translational modifications such as phosphorylation, acetylation and methylation play important roles in regulating the structures and functions of histones, which in turn regulate gene expression and DNA repair and replication. Histone modifying enzymes, such as deacetylases, methyltransferases and demethylases, have been pursued as therapeutic targets for various diseases. However, detection of the activities of these enzymes in high-throughput cell-based formats has remained challenging. We have developed high-throughput LanthaScreen® cellular assays for histone H3 site-specific modifications. These assays utilize cells expressing green fluorescence protein (GFP) tagged-histone H3 transiently delivered via BacMam and terbium labeled-anti-histone H3 modification-specific antibodies. Robust time-resolved Foerster resonance energy transfer signals were detected for H3 lysine-9 di-methylation (K9me2), lysine-4 di- (K4me2) and tri-methylation (K4me3) and lysine-27 tri-methylation (K27me3). Consistent with previous reports, hypoxic stress increased K4 methylation levels and methyltransferase G9a inhibitor UNC-0638 decreased K9me2 levels significantly with little effects on other modifications. Further validation of these assays using methyltransferases-specific RNAi oligos demonstrated that EZH2-specific RNAi reduced the level of K27me3 with little effect on the other three modifications, whereas G9a RNAi and SMYD3 RNAi reduced K9me2 and K4me2/3, respectively. The use of BacMam gene delivery system enables the measurement of these histone methylations in a variety of cell backgrounds including primary cells. In conclusion, we have developed homogenous cellular assays that can enable the high-throughput screening for modulators of histone H3 methylation at various lysine sites.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5006. doi:1538-7445.AM2012-5006
Abstract 501: The carboxypeptidase inhibitor TIG1 interacts with cathepsin L2 and inhibits cathepsin L2-stimulated cellular invasion
Authors: Jiang Shun-Yuan , Tsai Fu-Ming , Shyu Rong-Yaun , Wu Chang-Chieh , Tsai Tzung-Chieh , Wang Chun-Hua 
Published: August 2012

Abstract
The tazarotene-induced gene 1 (TIG1), also known as retinoic acid receptor responder 1 (RARRES1), is a putative tumor suppressor gene. The gene encodes a carboxypeptidase inhibitor for ATP/GTP binding protein-like 2 (AGBL2). This study identified TIG1 binding proteins and characterized the activities of TIG1 on cellular invasion of HCT116 colon cancer cells stimulated by the cathepsin L2 (CTSL2). The cytoplasmic portion of the TIG1A isoform was used for identification of TIG1 binding proteins using the yeast two-hybrid screening, and six genes, CTSL2, DNAJC8, SPATA22, SPINK2, VAC14, and C6orf225, were selected. CTSL2, a cysteine protease with an increased expression shown in breast and colon carcinomas, was selected for analysis. Immunoprecipitation analysis using transiently transfected cytosols confirmed the binding between both TIG1 isoforms and CTSL2. Both TIG1A and CTSL2 were secreted proteins; however, the interaction of both proteins in culture supernatants was not detected. Further immunoprecipitation analysis using purified recombinant proteins demonstrated direct binding between both TIG1 isoforms and CTSL2. Cellular invasion of HCT116 cells was increased by 52 to 71% in CTSL2 transiently transfected cells. Both TIG1 isoforms had no effects on cellular invasion of HCT116 cells. However, TIG1A and TIG1B significantly inhibited CTSL2-stimulated cellular invasion by 65.1 and 62.9%, respectively. In conclusion, both TIG1 isoforms interact with CTSL2 and inhibited CTSL2-stimulated cellular invasion of HCT116 cells. The results suggest that TIG1 may suppress CTSL2-mediated cellular invasion through inhibiting the activation of CTSL2 protease, and merit for further investigation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 501. doi:1538-7445.AM2012-501
Abstract 5014: Differences in DNA methylation pattern of primary bladder tumours correlate with their metastatic potential
Authors: Stubendorff Beatrice , Dudziec Ewa , Catto James , Sanjmyatav Jimsgene , Gaida Mieczyslaw , Wunderlich Heiko , Grimm Marc-Oliver , Junker Kerstin 
Published: August 2012

Abstract
Introduction: The prognosis for patients with metastatic bladder cancer is poor with a 5-year survival rate of only 6%. Early prediction of the metastatic risk in primary tumours can lead to improvements in prognosis and therapy. Currently, there are no parameters available that enable an individual risk assessment for patients with metastatic bladder cancer. Therefore, identification of new reliable prognostic markers for early prediction of tumour spread is required. The aim of this project is to determine whether changes in DNA methylation correlate with the metastasis risk and to identify a specific DNA methylation pattern that provides a reliable tool for prognosis assessment. Materials & methods: Genomic DNA was isolated from 23 invasive bladder tumour tissues with and without lymph node metastases. For enrichment of methylated fragments genomic DNA was incubated with 5-Methylcytosin antibody. Input and IP were labelled with Cy3 and Cy5. Labelled DNA was hybridizes onto CpG island microarrays. Cluster analysis enabled selection of differentially methylated candidate genes. The actual methylation state was confirmed by cleavage of genomic DNA with methylation dependent restriction enzyme (McrBc) followed by quantitative PCR. Results: In total, 201 promoter CpG islands show highly significant differences in DNA methylation between metastasised and non-metastasised primary bladder tumours (p&lt;0,01). In metastasised tumours 74 CpG islands are hypermethylated and 127 CpG islands are hypomethylated. Data base research for identification of candidate genes resulted in 61 hypermethylated and 58 hypomethylated genes that can clearly assigned to the identified promoter associated CpG islands. Validation of methylation level of candidate gene RASSF1 resulted in higher methylation in metastatic tumours (mean methylation: 38%) than in non-metastatic tumours (mean methylation: 26%). RASSF1 methylation shows strong correlation to T stage (r=0,65). Methylation of candidate gene KISS1R shows significant differences between patient groups (p=0,001). Mean methylation in metastatic tumours is 48% and in non-metastatic tumours 22%. Conclusion: Primary bladder tumours show significant differences in their DNA methylation pattern in correlation to their metastatic potential. KISS1R methylation is strongly associated with the metastatic risk of primary tumours. Further analysis will demonstrate the correlation between changes in DNA methyaltion and expression of corresponding genes. The impact of DNA methylation on tumour behaviour shall be determined in functional analysis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5014. doi:1538-7445.AM2012-5014
Abstract 5015: Regulation of histone modification and chromatin structure by p53-PADI4 pathway
Authors: Tanikawa Chizu , Nakamura Yusuke , Matsuda Koichi 
Published: August 2012

Abstract
Histone proteins are modified in response to various external signals, however their mechanisms are still not fully understood. We here report in vivo and in vitro citrullination of arginine 3 residue of histone H4 (H4R3) in response to DNA damage through the p53-PADI4 pathway. We also observed DNA damage-induced citrullination of lamin C through the p53-PADI4 pathway. Citrullinated H4R3 (cit-H4R3) and citrullinated lamin C are located around fragmented nuclei in apoptotic cells. Ectopic expression of PADI4 led to chromatin decondensation and promoted DNA cleavage, while Padi4-/- mice exhibited resistance to radiation-induced apoptosis in the thymus. We also found loss of function mutations of the PADI4 gene in several cancer cell lines. Furthermore, the level of cit-H4R3 was negatively correlated with that of p53 protein in cancer cells and with tumor size in non-small cell lung cancer tissues. Our findings reveal that citrullination of H4R3 would be an “apoptotic histone code” to detect damaged cells and induce nuclear fragmentation, which plays a crucial role in carcinogenesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5015. doi:1538-7445.AM2012-5015
Abstract 5022: Immune biology drives cancer specific methylation profiles in blood
Authors: Koestler Devin C. , Marsit Carmen J. , Christensen Brock C. , Accomando William , Langevin Scott M. , Houseman Eugene A. , Nelson Heather H. , Karagas Margaret R. , Wiencke John K. , Kelsey Karl T. 
Published: August 2012

Abstract
Blood leukocytes from patients with solid tumors exhibit complex and distinct cancer-associated patterns of DNA methylation. However, the biological mechanisms underlying these patterns remain poorly understood. Since epigenetic biomarkers offer significant clinical potential for cancer detection, we sought to address a mechanistic gap in recently published works, hypothesizing that this variation is in large part due to shifts in leukocyte populations. To discern differentially methylated regions (DMRs) among leukocyte subtypes, we assessed epigenome-wide DNA methylation in sorted, purified, healthy human peripheral blood leukocyte subtypes. Performing a targeted analysis of leukocyte DMRs from epigenome-wide blood methylation data in three independent case-control studies of different cancers revealed that leukocyte DMRs predict case status with a high degree of accuracy (area under the curve = 0.82, 0.83, and 0.67, forhead and neck squamous cell carcinoma (HNSCC), ovarian, and bladder cancer, respectively). These results demonstrate that blood-derived differences in DNA methylation patterns in patients with solid tumors are largely attributable to systematic differences in the DMRs that define specific, known leukocyte sub-populations, suggesting that the unique epigenetic signatures in blood from solid tumor patients arise as a result of immune responses represented by shifts in leukocyte populations.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5022. doi:1538-7445.AM2012-5022