bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 817: Assessment and manipulation of DNA methylation in cancer cells using terahertz radiation
Authors: Yang Hee-Jin , Cheon Hwayeong , Paik Jin Ho , Son Joo-Hiuk 
Published: August 2019

Abstract
Carcinogenesis is closely associated with abnormal regulation of gene expression, among which DNA methylation in one of the key epigenetic modifications. Therefore, several studies have been directed towards the evaluation of DNA methylation. Here, we aimed to experimentally observe the specific signal of methylated DNA in various blood cancer cell lines using terahertz (THz) radiation, which is presented as a resonance in the spectrum. THz radiations are electromagnetic waves having frequencies of 0.1−10 THz, which falls between those of infrared radiation and microwaves. Molecular low-energy motions in THz region, such as collective vibrations, torsion of molecular structures, and hydrogen bonds, is correlated with biological characteristics, i.e., vibrational modes of DNA, structural modes in proteins, cell membrane vibrations, or enzyme activity. These features are usually presented as a characteristic resonance of the modes in the THz spectrum. In our study, the degree of global DNA methylation was obtained by the quantification of the resonance around 1.7 THz, and the results were in good agreement with those obtained by enzyme-linked immunosorbent assay (ELISA). Further, DNA demethylation was performed using high-power THz radiation around the resonance frequency of 1.7 THz, which lead to a 10% to 72% decrease in the degree of DNA methylation as shown in Table 1. Thus, our data shows the feasibility of using THz radiation for the assessment and manipulation of DNA methylation. This is the first study wherein the sensing and manipulation of DNA methylation could be achieved using a non-contact and non-invasive optical technique. Use of THz radiation for the assessment of DNA methylation might be helpful for its rapid processing, while THz manipulation of DNA methylation can avoid the toxicity of chemical demethylating agents. We propose that THz radiation may be useful for the diagnosis of cancer and we expect that THz demethylation might find potential application in cancer therapy.
Change of methylation status of blood cancer DNA using high-power THz radiation.SamplesNo ExposureHigh-power THz exxpsoureChange (%) THzChange (%) ELISATHzELISARatio1THzELISARatio2119.621.8510.6111.661.0611.0040.5742.70211.341.388.2210.201.198.5710.0513.77315.151.4310.596.240.738.5558.8148.95417.731.4712.063.510.447.9880.2070.07511.271.437.8810.001.367.3511.274.90STDEV1.58STDEV1.24THz, the amplitude of terahertz resonance; ELISA, optical density of Enzyme linked immunosorbent assay; STDEV, standard deviation1 THz/ELISA of no exposure2 THz/ELISA of high-power THz exposure
Citation Format: Hee-Jin Yang, Hwayeong Cheon, Jin Ho Paik, Joo-Hiuk Son. Assessment and manipulation of DNA methylation in cancer cells using terahertz radiation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 817.
Abstract 820: Enzymatic Methyl-Seq: methylome analysis of challenging DNA samples
Authors: Williams Louise , Ponnaluri V K Chaithanya , Sexton Brittany S. , Saleh Lana , Marks Katherine , Samaranayake Mala , Ettwiller Laurence , Guan Shengxi , Church Heidi E. , Dai Nan , Tamanaha Esta , Yigit Erbay , Langhorst Bradley , Sun Zhiyi , Evans Thomas C. , Vaisvila Romualdas , Dimalanta Eileen , Davis Theodore B. 
Published: August 2019

Abstract
DNA isolated from blood draws (cell-free DNA (cfDNA)) or from archival material like formalin fixed paraffin embedded (FFPE) tissues have advanced the field of cancer genetics. DNA methylation (5-methylcytosines (5mC) and 5-hydroxymethylcytosines (5hmC)) is a key epigenetic factor that plays an important role in cellular processes and it’s misregulation results in diseased states like cancer. Advances in the field of sample preparation from biological matrices and genomics have enabled cancer biomarker identification based on methylation profiling.
Bisulfite sequencing is the standard method to detect methylation and has been employed for both targeted and whole genome methylation analysis. However, the chemical based bisulfite conversion of cytosines to uracils also results in DNA damage which subsequently results in shorter DNA insert sizes as well as introducing bias into the data. Robust biomarker detection relies primarily on the ability to profile methylation accurately. Analysis of DNA methylation from cfDNA and FFPE DNA is challenging as the DNA is typically of low quality and quantity. To overcome the drawbacks of bisulfite sequencing, we developed an enzyme based methylation detection technology, called NEBNext Enzymatic Methyl-Seq (EM-Seq). DNA damage is minimized enabling longer insert sizes, lower duplication rates and minimal GC bias resulting in more accurate quantification of methylation in the sample DNA.
Using EM-Seq, we profiled cfDNA and FFPE DNA from multiple tissue types. Results for these challenging DNA types showed that the EM-Seq libraries had longer inserts, lower duplication rates, higher percentages of mapped reads and less GC bias compared to WGBS libraries. These libraries also identified a higher number of CpG’s and the estimated global methylation levels were in good agreement with the absolute levels quantified using LC/MS. In conclusion, EM-Seq libraries have superior sequencing metrics resulting in robust methylation profiling for these types of challenging DNA samples.
Citation Format: Louise Williams, V K Chaithanya Ponnaluri, Brittany S. Sexton, Lana Saleh, Katherine Marks, Mala Samaranayake, Laurence Ettwiller, Shengxi Guan, Heidi E. Church, Nan Dai, Esta Tamanaha, Erbay Yigit, Bradley Langhorst, Zhiyi Sun, Thomas C. Evans, Romualdas Vaisvila, Eileen Dimalanta, Theodore B. Davis. Enzymatic Methyl-Seq: methylome analysis of challenging DNA samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 820.
Abstract 821: DNA hypermethylation of IRX4 is a frequent event that may confer growth advantage to pancreatic cancer cells
Authors: Chakma Kanchan , Gu Zhaodi , Motoi Fuyuhiko , Unno Michiaki , Horii Akira , Fukushige Shinichi 
Published: August 2019

Abstract
Epigenetic gene silencing by aberrant DNA methylation is one of the important mechanisms leading to the loss of key cellular pathways in tumorigenesis. Methyl-CpG targeted transcriptional activation (MeTA) reactivates hypermethylation-mediated silenced genes in a different way from DNA demethylating agents. Previous study using microarray coupled with MeTA (MeTA-array) identified seven commonly hypermethylation-mediated silenced genes in pancreatic cancer cell lines. In this study, IRX4 (Iroquois homeobox 4) was focused on because IRX4 was located at chromosome 5p15.33 where one of pancreatic cancer susceptibility loci has been identified through genome-wide association study (GWAS). IRX4 has also been identified as a candidate tumor suppressor gene in prostate cancer. IRX4 was greatly downregulated in all of the analyzed 12 pancreatic cancer cell lines by promoter hypermethylation. In addition, IRX4 promoter region was found to be frequently and specifically hypermethylated in primary resected pancreatic cancers (15/22: 68%); corresponding normal pancreatic tissues were unmethylated. To examine whether IRX4 has the growth inhibitory effect on pancreatic cancer cell lines, colony formation assay using PK-1 and PK-9 cell lines has been performed; compared with empty vector-transfected cells, IRX4 expression vector-transfected cells formed significantly reduced number of colonies. Furthermore, tetracycline-inducible IRX4 expressing vector system was constructed and a pancreatic cancer cell line PK-1 was analyzed for further functional investigation; induction of IRX4 suppressed cell growth in PK-1. Our results suggest that DNA methylation-mediated silencing of IRX4 is a frequent event that may confer growth advantage to pancreatic cancer cells and MeTA may be a powerful tool to search critical hypermethylated genes in tumorigenesis.
Citation Format: Kanchan Chakma, Zhaodi Gu, Fuyuhiko Motoi, Michiaki Unno, Akira Horii, Shinichi Fukushige. DNA hypermethylation of IRX4 is a frequent event that may confer growth advantage to pancreatic cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 821.
Abstract 835: Altered DNA modifications in Barrett’s oesophagus and oesophageal adenocarcinoma
Authors: Kriaucionis Skirmantas , Tomova Marketa , Kirschner Sophie , Brazauskas Pijus , Kgatle Mankgopo , Owen Richard , White Michael , Schuster-Boeckler Benjamin , Lu Xin 
Published: August 2019

Abstract
Cytosine in human DNA can be modified by DNA methyltransferases (DNMTs) and the Ten-Eleven Translocation (TET) family of oxygenases. Activity of these enzymes results in four modifications, among which 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are the major ones. Different patterns of localisation of both these modifications relate to gene transcription and the developmental origin of different cell types. Cancers have been shown to have globally altered DNA modifications, however it is poorly understood when in carcinogenesis the shift in DNA modifications happens and how it influences tumour growth. Here we mapped 5mC and 5hmC genome-wide at single nucleotide resolution in Barrett’s oesophagus, a well-known pre-malignant precursor of oesophageal adenocarcinoma (OAC). To get better insight into alterations in Barrett’s oesophagus (BO), we also analysed samples from OAC, adjacent normal oesophagus and gastric and duodenal epithelia. We found substantial global hypomethylation outside genic regions in Barrett’s oesophagus. Specific hypermethylation was evident in gene regulatory regions as defined by DNAseI hypersensitive sites. Moreover, we observed elevated methylation at CpG islands in a fraction of genes, which have reduced expression in Barrett’s oesophagus. While we find 5hmC depleted both in BO and OAC, distribution of the modification in CpG islands is different. Overall our results demonstrate that cancer-specific epigenetic alterations can already be found in benign Barrett’s oesophagus, suggesting early redistribution of DNA modifications in the process of transformation.
Citation Format: Skirmantas Kriaucionis, Marketa Tomova, Sophie Kirschner, Pijus Brazauskas, Mankgopo Kgatle, Richard Owen, Michael White, Benjamin Schuster-Boeckler, Xin Lu. Altered DNA modifications in Barrett’s oesophagus and oesophageal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 835.
Abstract 838: Epigenetic reprogramming of different cancer-related pathways at the single cell level after low-dose DNA demethylation therapy
Authors: Takeshima Hideyuki , Yoda Yukie , Watanabe Naoko , Wakabayashi Mika , Ushijima Toshikazu 
Published: August 2019

Abstract
The efficacy of DNA demethylation therapy is highly dependent on the dosing regimen. Administration of a drug at a dose much lower than the maximum tolerated dose (MTD) for a prolonged period shows a high therapeutic efficacy, despite its small demethylating effect. However, the mechanisms underlying the high therapeutic efficacy of low-dose treatment are still unclear. In this study, we aimed to reveal the mechanisms by analyzing decitabine (DAC)-treated individual cancer cells. To reveal the epigenetic reprogramming at the single cell level and its functional consequences, individual DAC-treated HCT116 cells (H3 clones) were cloned from DAC-treated bulk HCT116 cells. Genome-wide DNA methylation was analyzed using InfiniumHuman450 beadChip. In bulk cells, only partial reduction of DNA methylation levels was observed, and no genes were completely demethylated. In contrast, in cloned cells, a much larger reduction of DNA methylation levels was observed, depending upon genes. Promoter CpG islands of 233-470 genes of 1,188 hypermethylated genes in HCT116 were completely demethylated (Δβ ≥ 0.6) in some of the clones analyzed. Demethylated genes were highly variable among individual clones, and different cancer-related genes, such as those involved in the p53 pathway, WNT pathway, and cell cycle regulation, were completely demethylated, depending upon clones. For example, CDKN2A (p16) was completely demethylated only in a H3-32 clone, and this clone showed slower cell growth rate (14.6% of untreated cells), and aneuploid cells were detected possibly due to cellular senescence. These results showed that epigenetic reprogramming at the single cell level involves diverse cancer-related pathways, and this mechanism is likely to underlie the high efficacy of low-dose DNA demethylation therapy.
Citation Format: Hideyuki Takeshima, Yukie Yoda, Naoko Watanabe, Mika Wakabayashi, Toshikazu Ushijima. Epigenetic reprogramming of different cancer-related pathways at the single cell level after low-dose DNA demethylation therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 838.
Abstract 841: Meningioma subgroups associated with functional genomic elements defined by DNA methylation
Authors: Malta Tathiane M. , Snyder James , Wells Michael , deCarvalho Ana , Poisson Laila , Souza Camila , Zadeh Gelareh , Aldape Kenneth , Tirapelli Daniela , Carlotti Carlos , Lee Yan , Kalkanis Steven , Walbert Tobias , Noushmehr Houtan 
Published: August 2019

Abstract
Although most meningioma are non-malignant, there is a high recurrence rate among atypical and anaplastic (malignant) meningiomas (grades II/III). In addition, malignant meningioma usually progresses after treatment. Recently, based on DNA methylation, two subgroups of meningioma were described with recurrence-free survival differences. Epigenetic deregulation at distinct genomic elements can affect changes in gene expression and alter the transcriptional profile of the cancer cells. We seek to understand the mechanisms of meningioma recurrence and progression after initial treatment. In order to address this, we will use DNA methylation data to identify candidate noncoding elements and their connection with genes that might explain differences in meningioma prognostic subgroups. Using published DNA methylation data we compared favorable and unfavorable meningioma subgroups and identified 3,045 differentially methylated probes (p&lt; 0.0001, difference mean-methylation beta-value&gt; 0.2). Focusing on probes within known functional genomics, we identified 18 highly conserved genomic enhancers known to be activated in cancer that can potentially drive meningioma recurrence. We next investigated links between these enhancers and their targeted genes by incorporating GeneHancer annotation. We found that the unfavorable subgroup of meningiomas presented hypomethylation within enhancer regions that have the potential to target PARK7, ARID4B, and FBH1. ARID4B was previously shown to be highly active in high-grade meningiomas. We also identified 16 enhancer regions that overlap known prognostic cancer enhancer, previously identified in other tumor types. Our findings were validated in independent cohort comprised by public and unpublished DNA methylation datasets. Our preliminary results are the first to suggest that DNA methylation changes can be used to identify noncoding regions associated with meningioma prognosis. Identification of noncoding regions associated with meningioma recurrence will provide knowledge of the role of epigenomics in the development of malignant meningioma and of opportunities for targeted therapy.
Citation Format: Tathiane M. Malta, James Snyder, Michael Wells, Ana deCarvalho, Laila Poisson, Camila Souza, Gelareh Zadeh, Kenneth Aldape, Daniela Tirapelli, Carlos Carlotti, Yan Lee, Steven Kalkanis, Tobias Walbert, Houtan Noushmehr. Meningioma subgroups associated with functional genomic elements defined by DNA methylation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 841.
Abstract 842: Racial disparity in breast cancer: Tissue-specific epigenetic mechanisms
Authors: Lin Nan , Castle James , Liu Jinpeng , Shendre Aditi , Wang Chi , Liu Yunlong , He Chunyan 
Published: August 2019

Abstract
Racial disparity in breast cancer is well recognized. Compared with European American (EA) women, African American (AA) women have higher mortality rate despite low incidence rate, and they are more likely being diagnosed at younger age and with features that are more aggressive. Many risk factors of breast cancer, including social, culture, behavioral, genetics, and environmental factors, are disproportionally distributed across two racial groups. These factors could influence DNA methylation differently, as suggested by recent reports that describe biological differences of breast tumor in different racial group. However, no studies have systematically evaluate tissue-specific epigenetic mechanisms underlying the observed racial disparity in breast cancer development. We conducted a molecular epidemiological study of 276 EA and 186 AA healthy women. Genome-wide DNA methylation profiling was performed in normal breast tissue using the Illumina Methyl Captured EPIC-sequencing. Genome-wide association between race and DNA methylation identified differentially methylated sites near genes implicated in metastatic potential and aggressiveness of tumor, tamoxifen-resistance, immune response, and cancer-related metabolic pathways. Many of these genes have not been reported previously to be associated with breast cancer or racial disparities. Further analyses showed that differentially methylated sites across two racial groups were significantly overlapped with differentially methylated sites in tumor and normal breast tissue, suggesting tissue- and racial-specific epigenetic mechanisms underlying breast cancer development. Furthermore, meQTL analyses between known breast cancer risk loci and DNA methylation also suggested AA-specific risk loci were associated with DNA methylation sites implicated in metastatic potential and aggressiveness of tumor. Our study sheds light on tissue-specific genetic and epigenetic mechanisms underlying racial disparity in breast cancer. Further research is warranted to validate the findings in larger studies and to understand gene regulation network by linking with RNA-seq data.
Citation Format: Nan Lin, James Castle, Jinpeng Liu, Aditi Shendre, Chi Wang, Yunlong Liu, Chunyan He. Racial disparity in breast cancer: Tissue-specific epigenetic mechanisms [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 842.
Abstract 843: Epigenomic disruption of adipogenic regulators in dedifferentiated liposarcoma
Authors: Takamatsu Hironori , Hattori Naoko , Asano Naofumi , Iida Naoko , Yoshida Akihiko , Kobayashi Eisuke , Nakayama Robert , Matsumoto Morio , Nakamura Masaya , Kawai Akira , Ushijima Toshikazu 
Published: August 2019

Abstract
Well-differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas (DDLPS) are the most common soft-tissue sarcomas in adults. They develop as a result of a disturbance in adipogenic differentiation however, the epigenomic changes underlying liposarcomagenesis are unknown. Here, we aimed to elucidate the role of epigenomic alterations in the initiation of DDLPS. Genome-wide DNA methylation profiles of 15 liposarcoma (6 WDLPS and 9 DDLPS) samples and 6 normal adipose tissue samples were obtained using the Infinium MethylationEPIC BeadChip. After grouping neighboring probes into genomic blocks (GBs, &lt; 500 bp), principal component analysis of all the CpG GBs (n = 535,684) was conducted. Each of normal adipose tissue and WDLPS grouped closely while DDLPS distributed broadly, indicating heterogeneous methylation profiles among the DDLPS samples. Unsupervised hierarchical cluster analysis of enhancers (2,000 GBs with the high SD of 23,478 GBs) classified the samples into three tissue types, whereas that of promoters (1,000 GBs with the high SD of 8,668 GBs) could not classify the DDLPS samples distinctly. The Jonckheere-Terpstra trend test revealed 9,945 hypermethylated (p &lt; 0.01, Δβ &gt; 0.2) GBs in DDLPS compared to those in normal adipose tissues and WDLPS samples. Based upon a report on enhancers in adipocytes (Mikkelsen et al. Cell 143, 156-169. 2010), the hypermethylated GBs in DDLPS were enriched with typical- (2.2%: whole genome 1.2%) and super- (13.5%: whole genome 7.0%) enhancers. Genes involved in adipogenesis, including PPARG2, the master regulator of adipogenesis, and its target genes (FABP4 and PLIN1), were aberrantly methylated at the enhancers and repressed in DDLPS. Conversely, promoters were not enriched among hypermethylated GBs in DDLPS (1.2%: whole genome 4.1%). Taken together, these data indicate that aberrant methylation at the enhancers of adipogenic genes might be crucial for the generation of DDLPS. Evaluation of a demethylating agent in combination with a PPARγ agonist as a potential therapeutic is in progress.
Citation Format: Hironori Takamatsu, Naoko Hattori, Naofumi Asano, Naoko Iida, Akihiko Yoshida, Eisuke Kobayashi, Robert Nakayama, Morio Matsumoto, Masaya Nakamura, Akira Kawai, Toshikazu Ushijima. Epigenomic disruption of adipogenic regulators in dedifferentiated liposarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 843.