{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"study_type":["Cancer Genomics"],"full_dataset_link":["https://ega-archive.org/studies/EGAS00001000262"],"host":["EGA"],"description":["EGA study EGAS00001000262"],"dataset_title":["Batches 4-6 prostatectomy analysis","Title not provided","Normal prostatectomy project analysis and leftovers","Batches 1-3 prostatectomy analysis","The Natural History of Human Prostate Cancer","CRUK-ICGC Prostate DNA Methylation Sequencing Dataset (Prostatectomy Batches 1-6)","Non-ADT METs ICGC Prostate UK","ICGC Prostate Cancer Whole Genome Sequencing"],"repository":["EGA"],"category":["restricted"],"pubmed_abstract":["Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations. Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers. Computational chemogenomic (canSAR) analysis of prostate cancer mutations identified 11 targets of approved drugs, 7 targets of investigational drugs, and 62 targets of compounds that may be active and should be considered candidates for future clinical trials.","We report the first combined analysis of whole-genome sequence, detailed clinical history, and transcriptome sequence of multiple prostate cancer metastases in a single patient (A21). Whole-genome and transcriptome sequence was obtained from nine anatomically separate metastases, and targeted DNA sequencing was performed in cancerous and noncancerous foci within the primary tumor specimen removed 5 yr before death. Transcriptome analysis revealed increased expression of androgen receptor (AR)-regulated genes in liver metastases that harbored an AR p.L702H mutation, suggesting a dominant effect by the mutation despite being present in only one of an estimated 16 copies per cell. The metastases harbored several alterations to the PI3K/AKT pathway, including a clonal truncal mutation in PIK3CG and present in all metastatic sites studied. The list of truncal genomic alterations shared by all metastases included homozygous deletion of TP53, hemizygous deletion of RB1 and CHD1, and amplification of FGFR1. If the patient were treated today, given this knowledge, the use of second-generation androgen-directed therapies, cessation of glucocorticoid administration, and therapeutic inhibition of the PI3K/AKT pathway or FGFR1 receptor could provide personalized benefit. Three previously unreported truncal clonal missense mutations (ABCC4 p.R891L, ALDH9A1 p.W89R, and ASNA1 p.P75R) were expressed at the RNA level and assessed as druggable. The truncal status of mutations may be critical for effective actionability and merit further study. Our findings suggest that a large set of deeply analyzed cases could serve as a powerful guide to more effective prostate cancer basic science and personalized cancer medicine clinical trials."],"pubmed_title":["Integrated clinical, whole-genome, and transcriptome analysis of multisampled lethal metastatic prostate cancer.","Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets."],"pubmed_authors":["Wedge David C DC, Gundem Gunes G, Mitchell Thomas T, Woodcock Dan J DJ, Martincorena Inigo I, Ghori Mohammed M, Zamora Jorge J, Butler Adam A, Whitaker Hayley H, Kote-Jarai Zsofia Z, Alexandrov Ludmil B LB, Van Loo Peter P, Massie Charlie E CE, Dentro Stefan S, Warren Anne Y AY, Verrill Clare C, Berney Dan M DM, Dennis Nening N, Merson Sue S, Hawkins Steve S, Howat William W, Lu Yong-Jie YJ, Lambert Adam A, Kay Jonathan J, Kremeyer Barbara B, Karaszi Katalin K, Luxton Hayley H, Camacho Niedzica N, Marsden Luke L, Edwards Sandra S, Matthews Lucy L, Bo Valeria V, Leongamornlert Daniel D, McLaren Stuart S, Ng Anthony A, Yu Yongwei Y, Zhang Hongwei H, Dadaev Tokhir T, Thomas Sarah S, Easton Douglas F DF, Ahmed Mahbubl M, Bancroft Elizabeth E, Fisher Cyril C, Livni Naomi N, Nicol David D, Tavaré Simon S, Gill Pelvender P, Greenman Christopher C, Khoo Vincent V, Van As Nicholas N, Kumar Pardeep P, Ogden Christopher C, Cahill Declan D, Thompson Alan A, Mayer Erik E, Rowe Edward E, Dudderidge Tim T, Gnanapragasam Vincent V, Shah Nimish C NC, Raine Keiran K, Jones David D, Menzies Andrew A, Stebbings Lucy L, Teague Jon J, Hazell Steven S, Corbishley Cathy C, de Bono Johann J, Attard Gerhardt G, Isaacs William W, Visakorpi Tapio T, Fraser Michael M, Boutros Paul C PC, Bristow Robert G RG, Workman Paul P, Sander Chris C, Hamdy Freddie C FC, Futreal Andrew A, McDermott Ultan U, Al-Lazikani Bissan B, Lynch Andrew G AG, Bova G Steven GS, Foster Christopher S CS, Brewer Daniel S DS, Neal David E DE, Cooper Colin S CS, Eeles Rosalind A RA","Bova G Steven GS, Kallio Heini M L HM, Annala Matti M, Kivinummi Kati K, Högnäs Gunilla G, Häyrynen Sergei S, Rantapero Tommi T, Kivinen Virpi V, Isaacs William B WB, Tolonen Teemu T, Nykter Matti M, Visakorpi Tapio T"],"name_synonyms":["hereditary prostate cancer, cancer of the prostate, grupo, Prostate Neoplasms, ensemble, Neoplasms, familial, Rest, study., Cancers, cancer of prostate, Prostate Neoplasm, group, set, Prostatic Neoplasm, Cancer of the Prostate, grupos, Prostatic Cancer, Neoplasm, Prostatic Cancers, Prostatic, prostate cancer, PC, NOS, Cancer of Prostate, Prostate Cancer, groupe, Prostate, Gruppe, Cancer, Prostate Cancers"],"description_synonyms":["MPS2, insensitive, Activity, Product, single-organism developmental process, Prostate Neoplasms, Laboratory, Transcriptome Profile, AI461847, acetylglucosaminyltransferase-like protein, Neoplasms, postnatal development, Benign Neoplasm, Mbp1, Gene Expression Profile, Gene, growth and development, Profiles, Tumor, Malignant, LARGE1, froggy, Gyltl1a, DOI, Publication, Pharmaceutical Product, Prostatic Cancers, Ethnic Group, Pgi, Research Activity, Gpi-1, Cancer of Prostate, myd, Laboratory Research, Gonadectomies, Prostate Cancers, doi, Priorities, Drugs, study, SIDS, like-acetylglucosaminyltransferase, Malignancy, Genomes, Research, Gpi-1r, Nlk, MDDGB6, Gpi-1s, Profile, Phi, Gpi-1t, Mbp-1, LARGE, Signatures, c-ros-1, Neoplasias, BPFD#36, set, Prostatic Neoplasm, drugs, Cancer of the Prostate, malignant neoplasm, grupos, Expression Signature, medicine, Pharmaceutical, sample, heterogeneity, Nationality, Transcriptomes, Prostatic, Malignancies, Development and Research, Research Priority, Preparation, Cancer, Tumors, Pharmaceuticals, NK/GPI, hereditary prostate cancer, Gpi, Products, cancer of the prostate, Prostates, Transcriptome, Malignant Neoplasm, grupo, Data Set, gyltl1b-b, drug, Expression Profiles, familial, Ethnic Groups, Research Priorities, MF, Ids, Amf, group, metastatic neoplasm, Literatures, Gene Expression, development, metastatic disease, Priority, MT, Benign, mOC-X, male prostate, MDDGA6, Expression Signatures, mKIAA0609, Prostatic Cancer, Gene Expression Signatures, Research Activities, Neoplasm, NOS, Pharmaceutic, Ids., Gene Expression Signature, NK|GPI, ROS, KIAA0609, Expression Profile, acetylglucosaminyltransferase-like 1A, NK, Transcriptome Profiles, Gonadectomy, Research and Development, fg, Castrations, primary cancer, Org, ORG, gyltl1b, resistant, ensemble, Pharmaceutic Preparations, postnatal growth, mdc1d, Rest, Benign Neoplasms, Gpi1-r, Nationalities, Gpi1-s, Cancers, whole genome, Gpi1-t, cancer of prostate, LARGE_HUMAN, malignant tumor, sample population, Prostate Neoplasm, Malignant Neoplasms, Activities, Drug, MDC1D, Preparations, MCF3, like-glycosyltransferase, enr, Gene Expression Profiles, metastatic tumor, metastatic tumour, prostate cancer, PC, Signature, Pharmaceutical Products, Prostate Cancer, prostate, growth, groupe, Neoplasia, Bglap-rs1, Prostate, prostata, Gruppe, Pharmaceutical Preparation, glycosyltransferase-like protein LARGE1, Gpi1s"],"pubmed_title_synonyms":["metastatic prostate cancer., Transcriptome, metastatic prostate carcinoma, Genomes, determination, Transcriptome Profile, Profile, Expression Profiles, Gene Expression Profile, Gene, whole genome, Profiles, prostate cancer metastatic, Signatures, Gene Expression, Expression Signature, Gene Expression Profiles, Expression Signatures, Gene Expression Signatures, chemical analysis, Transcriptomes, Gene Expression Signature, assay, Signature, Expression Profile, prostate carcinoma metastatic, Transcriptome Profiles"],"pubmed_abstract_synonyms":["HNF3-alpha, other disease, New Drug, joints, Materials, single-organism developmental process, Product, Prostate Neoplasms, determination, GLM3, tFoxA1, Neoplasms, postnatal development, Investigational New, DmelCG30169, Benign Neoplasm, Gene, growth and development, Tumor, Malignant, CG30169, temporal, metastatic prostate cancer, Mutations, AW555109, BcDNA:SD25109, diseases, Joint, Core Genome, foxa1, AI851787, Pharmaceutical Product, Prostatic Cancers, Familiar breast and Ovarian cancer syndrome, disease or disorder, diseases and disorders, tcf3a, DmF2, FANCD1, BROVCA2, Cancer of Prostate, Fs(3)Hor, Prostate Cancers, lod, Drugs, hnf3a, human disease, DmelCG2684, Investigational., metastatic prostate carcinoma, Genetic, FAD1, Genomes, BRCC2, Malignancy, Tcf3a, Accessory Genome, HNF3alpha, dCHD1, New Drugs, NTef2, Investigational Drug, chd1, PNCA2, non-neoplastic, Hnf-3a, Neoplasias, Prostatic Neoplasm, drugs, Cancer of the Prostate, malignant neoplasm, medicine, FANCB, Pharmaceutical, FANCD, articular joint, Prostatic, disorder, Homo sapiens disease, Malignancies, Investigational Drugs, HNF3A, Preparation, RAB163, FACD, incidence, CG3733, prostate carcinoma metastatic, Cancer, Tumors, Pharmaceuticals, hereditary prostate cancer, Dissections, hereditary breast ovarian cancer, Products, joint, cancer of the prostate, Malignant Neoplasm, BRCA1, BRCA2, CHD1, familial, disorders, DmCHD1, medical condition, prostate cancer metastatic, Medications, Investigational New Drugs, Cistrons, Pangenome, Tcf-3a, CG13583, CG13584, Fs(3)Sz11, development, Hnf3a, MT, Benign, Investigational New Drug, Prostatic Cancer, chemical analysis, Diseases, Neoplasm, condition, Genetic Materials, CHD-1, NOS, Pharmaceutic, XRCC11, Genetic Material, Investigational, primary cancer, articulation, DmelCG3733, Pharmaceutic Preparations, postnatal growth, 30169, dmbrca2, Benign Neoplasms, l(2)23Cd, Cancers, TCF3A, Lds, cancer of prostate, malignant tumor, Prostate Neoplasm, brca2, early, 4930525N21Rik, Malignant Neoplasms, loss of, Fancd1, Drug, AI256696, disease, Preparations, Pan-genome, FAD, Material, Horka, AW045498, CG2684, Fs(3)Horka, prostate cancer, PC, Cistron, assay, Pharmaceutical Products, Prostate Cancer, growth, Neoplasia, Prostate, Pharmaceutical Preparation"],"additional_accession":[]},"is_claimable":false,"name":"CRUK-ICGC Prostate Cancer Group Study","description":"Prostate cancer somatic genomic sequencing data generated from 2011 onwards under auspices of the International Cancer Genome Consortium Prostate Cancer UK consortium (CRUK-ICGC Prostate Group), co-led by Colin Cooper and Ros Eeles, with other Principal Investigators (Brewer, Neal, Bova, McDermott, Wedge, Lynch, Massie, and Foster) and others as listed in study publications. Funded by Cancer Research UK and other funders as listed in study publications.  Contents and publications related to each dataset are described with each dataset (EGAD) entry.\nOur study was funded with the ambition of collecting Whole Genome DNA sequence data from 250 prostate cancers, with matching transcriptome and methylome data.\n The original aims of the project were:\n1.To understand the significance of multifocal prostate cancer. \n2.To understand the clinical heterogeneity of prostate cancer to devise markers for predicting outcome and for drug targeting.\n3.To understand the molecular basis of development and spread of castration-resistant and metastatic disease \n4.To understand the aetiology of prostate cancer particularly the large variation in incidences that occur in different populations and ethnic groups. \nPlease see https://doi.org/10.5281/zenodo.4022439 for links between sample IDs reported in literature and EGA IDs.","dates":{"updated":"2023-04-13 11:23:16"},"accession":"EGAS00001000262","cross_references":{"TAXONOMY":["9606"],"pubmed":["29662167","27148588"],"EGA":["EGAD00001000891","EGAD00001000263","EGAD00001000892","EGAD00010000498","EGAD00001003225","EGAD00001000689","EGAD00001010184","EGAD00001002002","EGAD00001004125","EGAD00001001116","EGAC00001000010"]}}