{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"dataset_type":["N/A"],"full_dataset_link":["https://ega-archive.org/datasets/EGAD00010001596"],"sample_count":["32"],"description":["EGA dataset EGAD00010001596"],"repository":["EGA"],"title":["DNA methylation of Rhabdomyosarcoma tumors"],"pubmed_abstract":["<h4>Background</h4>Telomeres are the protective arrays of tandem TTAGGG sequence and associated proteins at the termini of chromosomes. Telomeres shorten at each cell division due to the end-replication problem and are maintained above a critical threshold in malignant cancer cells to prevent cellular senescence or apoptosis. With the recent advances in massive parallel sequencing, assessing telomere content in the context of other cancer genomic aberrations becomes an attractive possibility. We present the first comprehensive analysis of telomeric DNA content change in tumors using whole-genome sequencing data from 235 pediatric cancers.<h4>Results</h4>To measure telomeric DNA content, we counted telomeric reads containing TTAGGGx4 or CCCTAAx4 and normalized to the average genomic coverage. Changes in telomeric DNA content in tumor genomes were clustered using a Bayesian Information Criterion to determine loss, no change, or gain. Using this approach, we found that the pattern of telomeric DNA alteration varies dramatically across the landscape of pediatric malignancies: telomere gain was found in 32% of solid tumors, 4% of brain tumors and 0% of hematopoietic malignancies. The results were validated by three independent experimental approaches and reveal significant association of telomere gain with the frequency of somatic sequence mutations and structural variations.<h4>Conclusions</h4>Telomere DNA content measurement using whole-genome sequencing data is a reliable approach that can generate useful insights into the landscape of the cancer genome. Measuring the change in telomeric DNA during malignant progression is likely to be a useful metric when considering telomeres in the context of the whole genome.","Rhabdomyosarcoma is a soft-tissue sarcoma with molecular and cellular features of developing skeletal muscle. Rhabdomyosarcoma has two major histologic subtypes, embryonal and alveolar, each with distinct clinical, molecular, and genetic features. Genomic analysis shows that embryonal tumors have more structural and copy number variations than alveolar tumors. Mutations in the RAS/NF1 pathway are significantly associated with intermediate- and high-risk embryonal rhabdomyosarcomas (ERMS). In contrast, alveolar rhabdomyosarcomas (ARMS) have fewer genetic lesions overall and no known recurrently mutated cancer consensus genes. To identify therapeutics for ERMS, we developed and characterized orthotopic xenografts of tumors that were sequenced in our study. High-throughput screening of primary cultures derived from those xenografts identified oxidative stress as a pathway of therapeutic relevance for ERMS."],"pubmed_title":["Assessing telomeric DNA content in pediatric cancers using whole-genome sequencing data.","Targeting oxidative stress in embryonal rhabdomyosarcoma."],"pubmed_authors":["Chen Xiang X, Stewart Elizabeth E, Shelat Anang A AA, Qu Chunxu C, Bahrami Armita A, Hatley Mark M, Wu Gang G, Bradley Cori C, McEvoy Justina J, Pappo Alberto A, Spunt Sheri S, Valentine Marcus B MB, Valentine Virginia V, Krafcik Fred F, Lang Walter H WH, Wierdl Monika M, Tsurkan Lyudmila L, Tolleman Viktor V, Federico Sara M SM, Morton Chris C, Lu Charles C, Ding Li L, Easton John J, Rusch Michael M, Nagahawatte Panduka P, Wang Jianmin J, Parker Matthew M, Wei Lei L, Hedlund Erin E, Finkelstein David D, Edmonson Michael M, Shurtleff Sheila S, Boggs Kristy K, Mulder Heather H, Yergeau Donald D, Skapek Steve S, Hawkins Douglas S DS, Ramirez Nilsa N, Potter Philip M PM, Sandoval John A JA, Davidoff Andrew M AM, Mardis Elaine R ER, Wilson Richard K RK, Zhang Jinghui J, Downing James R JR, Dyer Michael A MA","Parker Matthew M, Chen Xiang X, Bahrami Armita A, Dalton James J, Rusch Michael M, Wu Gang G, Easton John J, Cheung Nai-Kong NK, Dyer Michael M, Mardis Elaine R ER, Wilson Richard K RK, Mullighan Charles C, Gilbertson Richard R, Baker Suzanne J SJ, Zambetti Gerard G, Ellison David W DW, Downing James R JR, Zhang Jinghui J"],"name_synonyms":["DNA methylation maintenance, Malignant Neoplasm, Malignancy, malignant, Neoplasms, Rhabdomyosarcomas, Benign Neoplasm, Benign Neoplasms, DNA Methylations, Cancers, DNA methylation, Tumor, Malignant, rhabdomyosarcoma, Neoplasias, Benign, Neoplasm, Malignancies, DNA, rhabdomyosarcoma (disease), Methylations, Methylation, Neoplasia, Cancer, Tumors, Malignant Neoplasms."],"description_synonyms":["rostral migratory pathway, DNA methylation maintenance, Malignant Neoplasm, Malignancy, Neoplasms, Benign Neoplasm, Benign Neoplasms, patient, DNA Methylations, Cancers, DNA methylation, Tumor, Malignant, Client, Neoplasias, Benign, Patient, Clients, Neoplasm, Malignancies, DNA, RMS, other neoplasm, Methylations, Methylation, Neoplasia, Cancer, Tumors, Malignant Neoplasms."],"pubmed_title_synonyms":["Neoplasias, MT, Benign, Malignant Neoplasm, Malignancy, Neoplasms, telomeric DNA, Neoplasm, Benign Neoplasm, Malignancies, Benign Neoplasms, INSDC_feature:telomere, Cancers, whole genome, Tumor, telomeric sequence, Malignant, Neoplasia, Cancer, Tumors, Malignant Neoplasms, Genomes."],"pubmed_abstract_synonyms":["telomere, determination, Flagyl, Blood, Brain Neoplasms, Phases, Cellular Aging, Aging, Measure, Tumor, Brain Metastases, Divisions, Metronidazole Hydrochloride, Mutations, Extrinsic Pathway Apoptoses, INTRACRANIAL NEOPL, Associations, nuclear chromosome, tumour of brain, protective, average, Senescence, thymus nucleic acid, M Phases, Genomes, brain neoplasms, M, Brain Malignant Neoplasms, Weights, Primary Brain Tumors, Brain Tumor, Division Phase, Intrinsic Pathway Apoptosis, Ageing, neoplasm of brain, Replicative, Brain Neoplasm, Primary Malignant Brain Tumors, MetroGel, malignant neoplasm, Classic, scientific observation, Recurrent Brain Tumor, Classical Apoptosis, Malignancies, Double-Stranded DNA, deoxyribonucleic acids, INSDC_feature:telomere, DNAn, Tumors, Intracranial Neoplasm, brain neoplasm, Malignant Brain Neoplasms, Caspase-Dependent Apoptosis, Brain Benign Neoplasm, frequency, Metronidazole Phosphate, Malignant Primary Brain Neoplasms, Primary Brain Neoplasm, Double-Stranded, NEOPL BRAIN, Cell Divisions, telomeric sequence, Primary Brain Tumor, (Deoxyribonucleotide)n+m, Benign, signaling (initiator) caspase activity, Brain Benign Neoplasms, induction of apoptosis, Trichopol, Satric, Intrinsic Pathway, Extrinsic Pathway Apoptosis, Brain Malignant Neoplasm, Clont, Malignant Primary Brain Tumors, Cellular, Hematopoietic Malignancies, Vagilen, Metronidazole Monohydrochloride, Caspase-Dependent, desoxyribose nucleic acid, END, Malignant Brain Neoplasm, Primary Malignant, Hematopoietic, Cancer of the Brain, decrease in risk, Benign Neoplasms, whole genome, tumor of the Brain, Hematologic Malignancies, surveillance, morbidity, Malignant Neoplasms, Intrinsic Pathway Apoptoses, Intracranial, Trivazol, neoplasm of the brain, induction of apoptosis by p53, Chromosome, brain tumor, ds DNA, telomeric DNA, 2-methyl-5-nitro-, Extrinsic Pathway, Hematologic Neoplasm, Measures and Weights, 1H-Imidazole-1-ethanol, DNA, other neoplasm, Trichazol, Classical, Metric, Apoptoses, Brain, Brain Tumors, telomeric region, Primary Malignant Brain Neoplasms, DNS, Cell Aging, (Deoxyribonucleotide)n, Neoplasms, Primary Brain Neoplasms, Cancer of Brain, caspase-dependent programmed cell death, Benign Neoplasm, Gene, Caspase Dependent Apoptosis, Metrodzhil, Malignant, Deoxyribonucleic acids, Hematopoietic Neoplasm, Hematopoietic Malignancy, Recurrent Brain Tumors, Deoxyribonucleic Acid, Recurrent, Core Genome, Blood Cancers, Gene Products, whole genome., Type I, Hematological Malignancy, Metronidazole Phosphoester, Cell Ageing, telomeres, Cell Division Phase, tumour of the Brain, Malignancy, occurrence, Replicative Senescence, Accessory Genome, prevalence, Danizol, Measures, Double Stranded, Cell Division, Deoxyribonucleic acid, Hematopoietic Neoplasms, Division, apoptosis activator activity, Cell Senescence, Neoplasias, 2 Methyl 5 nitroimidazole 1 ethanol, Hematological Neoplasms, PRIMARY BRAIN NEOPL, Hematologic Malignancy, Gineflavir, Classic Apoptosis, (Deoxyribonucleotide)m, HHT1, tumor of brain, incidence, NEOPL INTRACRANIAL, Cancer, Apoptosis, Hematological Malignancies, measuring, Malignant Neoplasm, Edg, DNAn+1, Proteins, Benign Brain Neoplasms, Cellular Ageing, Hematologic, Primary, 2-Methyl-5-nitroimidazole-1-ethanol, Hematological Neoplasm, Pangenome, Cell, MT, Programmed Cell Death, Protein, chemical analysis, Neoplasm, Telomeres, sequence, Brain Cancers, Bayer 5360, ds-DNA, Brain Metastase, M Phase, outbreaks, Intracranial Neoplasms, Phase, primary cancer, brain neoplasm (disease), apoptosis, Scales, Blood Cancer, Cancers, Brain Cancer, malignant tumor, primary structure of sequence macromolecule, endemics, Metrogyl, Protein Gene Products, Classic Apoptoses, Gene Proteins, Pan-genome, Hematological, Desoxyribonukleinsaeure, commitment to apoptosis, Benign Brain Neoplasm, epidemics, assay, brain tumour, ORW1, Neoplasia"],"additional_accession":[]},"is_claimable":false,"name":"DNA methylation of Rhabdomyosarcoma tumors","description":"DNA methylation data from patient RMS tumor samples from Illumina 450 K arays","dates":{"updated":"2019-08-05 17:30:56"},"accession":"EGAD00010001596","cross_references":{"TAXONOMY":["9606"],"pubmed":["23232254","24332040"],"EGA":["EGAC00001000044","EGAS00001000256"]}}