EGAGenomicsIllumina HiSeq 2000;https://ega-archive.org/datasets/EGAD0000100200978EGA dataset EGAD00001002009EGAThe clinical heterogeneity of prostate cancer (PCa) makes it difficult to identify those patients that could benefit from more aggressive treatments. As a contribution to a better understanding of the genomic changes in the primary tumor that are associated with the development of high-risk disease, we performed exome sequencing and copy number determination of a clinically homogeneous cohort of 47 high-risk PCas. We confirmed recurrent mutations in SPOP, PTEN and TP53 among the 850 point mutations we detected. In seven cases, we discovered genomic aberrations in the TET1 (Ten-Eleven Translocation 1) gene which encodes a DNA hydroxymethylase than can modify methylated cytosines in genomic DNA and thus is linked with gene expression changes. TET1 protein levels were reduced in tumor versus non-tumor prostate tissue in 39 of 40 cases. The clinical relevance of changes in TET1 levels was demonstrated in an independent PCa cohort, in which low TET1 mRNA levels were significantly associated with worse metastases-free survival. We also demonstrate a strong reduction in hydroxymethylated DNA in tumor tissue in 27 of 41 cases. Furthermore, we report the first exploratory (h)MeDIP-Seq analyses of eight high-risk PCa samples. This reveals a large heterogeneity in hydroxymethylation changes in tumor versus non-tumor genomes which can be linked with cell polarity.Genomic and epigenomic analysis of high-risk prostate cancer reveals changes in hydroxymethylation and TET1.Spans Lien L, Van den Broeck Thomas T, Smeets Elien E, Prekovic Stefan S, Thienpont Bernard B, Lambrechts Diether D, Karnes R Jeffrey RJ, Erho Nicholas N, Alshalalfa Mohammed M, Davicioni Elai E, Helsen Christine C, Gevaert Thomas T, Tosco Lorenzo L, Haustermans Karin K, Lerut Evelyne E, Joniau Steven S, Claessens Frank FVasp, VASP, DmelCG15112, ENHANCER OF ATNSI ACTIVITY, RAB8, Mouse Erythroleukemia cell line, AA409338, Data Set, MENA, NDPP1, melorheostosis, isolated., l(2)02029, MEL, Mel, Enb, enb, ENA, Ena, CG15112, ENA/VASPhereditary prostate cancer, WES, Complete Transcriptome, cancer of the prostate, Complete, Complete Transcriptome Sequencing, Exome Sequencings, Complete Exome Sequencings, Risk, Prostate Neoplasms, Complete Exome, Complete Exome Sequencing, Neoplasms, Whole Transcriptome Sequencing, Exome, Risks, familial, Cancers, cancer of prostate, Sequencing, Prostate Neoplasm, Prostate Cancers., Relative, Exome Sequencing, Prostatic Neoplasm, Whole Exome, Cancer of the Prostate, Whole, Relative Risks, Prostatic Cancer, Whole Exome Sequencing, Neoplasm, Prostatic Cancers, Prostatic, prostate cancer, PC, NOS, Whole Transcriptome, Transcriptome Sequencing, Cancer of Prostate, Transcriptome Sequencings, Prostate Cancer, Prostate, Relative Risk, CancerLCX, bA119F7.1., hereditary prostate cancer, cancer of the prostate, MZA15_11, Risk, determination, Prostate Neoplasms, Neoplasms, CXXC6, Risks, familial, 2510010B09Rik, Cancers, MZA15.11, cancer of prostate, Prostate Neoplasm, Cxxc6, Relative, Prostatic Neoplasm, AA517754, D10Ertd17e, Cancer of the Prostate, TET1, BB001228, chemical analysis, Relative Risks, Prostatic Cancer, TETRASPANIN 1, Neoplasm, Prostatic Cancers, Prostatic, prostate cancer, PC, NOS, assay, mKIAA1676, Cancer of Prostate, TORNADO 2, Prostate Cancer, Prostate, Relative Risk, Cancer, Prostate Cancersl(3)j4C7, 0869/09, Materials, single-organism developmental process, Methylated DNA Immunoprecipitation sequencing, l(3)2004, acetylglucosaminyltransferase-like protein, postnatal development, Polarities, DPTEN, Mbp1, growth and development, Progress Reports, Tumor, establishment and/or maintenance of cell polarization, Tp53, Dmel_CG9924, Cxxc6, Mutations, Relative, Readability, diseases, Summary Report, BTBD32, bbl, diseases and disorders, Whole Transcriptome, Transcriptome Sequencing, TEP1, myd, Non Polyadenylated, Summary Reports, Benson syndrome, mei-P19, strong, amyloidosis, human disease, thymus nucleic acid, me75, Pca-1, Gene Expressions, like-acetylglucosaminyltransferase, BCC7, Progress Report, Genomes, D-SPOP, Complete Exome Sequencing, Polyadenylated Messenger, Whole Transcriptome Sequencing, Tissue, hypoplasia, Mbp-1, twy, D17Mit170, free, T1, Progress, Prostatic Neoplasm, Cancer of the Prostate, Rdx, Field Reports, BB001228, Therapies, Homo sapiens disease, Malignancies, Double-Stranded DNA, deoxyribonucleic acids, mKIAA1676, DNAn, TL, Tumors, Therapy, cell polarity., cancer of the prostate, Prostates, l(3)88Aa, Polyadenylated, gyltl1b-b, Pdnp1, Exome, familial, arteria cerebri communicans posterior, DmelCG12537, 2510010B09Rik, familial cutaneous lichen, Double-Stranded, Tl3, Tl2, (Deoxyribonucleotide)n+m, 4833416E15Rik, C76301, Benign, PTEN3, TET1, Investigative Report, PTEN1, MDDGA6, mKIAA0609, Relative Risks, Pca, PCA, Diseases, TETRASPANIN 1, POSTERIOR, l(3)A6, Genetic Materials, NOS, bfy, simple tissue, desoxyribose nucleic acid, KIAA0609, AXPC1, Genetic Material, acetylglucosaminyltransferase-like 1A, Polyadenylated Messenger RNA, PCS, fg, Complete Transcriptome, Non Polyadenylated mRNA, gyltl1b, protein_coding_transcript, Risk, death rate, MMAC1, Field, mdc1d, Anaphylaxis, Benign Neoplasms, INSDC_feature:gene, SPOP, Polarity, PTENa, cancer of prostate, LARGE_HUMAN, Treatments, Non-Polyadenylated mRNA, Malignant Neoplasms, disease, MDC1D, BEST:GM07940, D10Ertd17e, Report, enr, Patient, Material, ds DNA, Whole Exome Sequencing, P53, p44, PC-1, bhy, Cistron, DNA, other neoplasm, Transcriptome Sequencings, TEF2, BZS, prostate, Ly-41, Poly(A) RNA, Prostate, prostata, 2310035O07Rik, protein levels, other disease, Passive, CD203c, l(3)SG40, MZA15_11, NPP1, DNS, Prostate Neoplasms, (Deoxyribonucleotide)n, Complete Exome, GLM2, Neoplasms, p53, Benign Neoplasm, number, Gene, MZA15.11, Malignant, LFS1, presence, LARGE1, Deoxyribonucleic acids, froggy, gDNA, Gyltl1a, MHAM, Investigative, establishment and/or maintenance of cell polarity, Deoxyribonucleic Acid, reduced, resilient, Messenger, tough, Core Genome, AI463227, Prostatic Cancers, disease or disorder, l(3)j1D1, Low, l(3)S086909, tiny, Cancer of Prostate, Spop, Prostate Cancers, Npps, Passive Cutaneous, FLVCR, l(3)03477, WES, Complete, Exome Sequencings, Genetic, Malignancy, l(3)dsl-6, MDDGB6, biparietal Alzheimer disease, Accessory Genome, Pcif1, Double Stranded, messenger RNA, Deoxyribonucleic acid, LARGE, lichen amyloidosis, Expressions, DmelCG5671, Sequencing, non-neoplastic, HIB, Neoplasias, BPFD#36, template RNA, Whole Exome, Trp53, time of survival, Clients, Whole, heterogeneity, B430203M17Rik, Prostatic, disorder, MFSD7B, (Deoxyribonucleotide)m, Expression, TRP53, Investigative Reports, TORNADO 2, Cancer, hib, small, hereditary prostate cancer, CG10235, RNA, CG12537, Malignant Neoplasm, Complete Exome Sequencings, PTEN, cou, AI315626, DNAn+1, disorders, CG9924, Point Mutations, Messenger RNA, dPten, medical condition, pten, Cistrons, Client, Pangenome, Cell, Cutaneous Anaphylaxis, Xp53, bA119F7.1, development, M6S1, Exome Sequencing, count in organism, dpten, Lr, survival, AI428932, male prostate, Poly(A)+ mRNA, CWS1, Prostatic Cancer, Research Reports, Neoplasm, anon-WO0118547.577, INSDC_feature:mRNA, condition, Polyadenylated RNA, dPTEN, ds-DNA, Mutation, Relative Risk, LCX, Poly(A)+ RNA, Mmac, Complete Transcriptome Sequencing, 10q23del, CG5671, underdeveloped, mRNA, Poly(A) Tail, CXXC6, Risks, postnatal growth, Cell Polarities, choanal atresia, Non-Polyadenylated, Cancers, Understanding, Dromel_CG9924_FBtr0082871_rdx_mORF, A130070J02Rik, l(3)dsl6, Prostate Neoplasm, DEC, AA517754, Pan-genome, like-glycosyltransferase, Therapeutic, Reports, PCARP, Point, cardinality, Desoxyribonukleinsaeure, Bra, prostate cancer, PC, Treatment, E-NPP1, ttw, Polyadenylated mRNA, Summary, Prostate Cancer, growth, Neoplasia, Field Report, glycosyltransferase-like protein LARGE1falseena-DATASET-KU-MEL-12-04-2016-11:46:48:538-274 - samplesExome sequencing of high-risk prostate cancer2017-07-26 15:39:27EGAD00001002009960627014907EGAC00001000260EGAS00001001015