{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"technology_type":["Illumina MiSeq"],"study_type":["Other"],"full_dataset_link":["https://ega-archive.org/studies/EGAS00001000451"],"host":["EGA"],"description":["EGA study EGAS00001000451"],"dataset_title":["Plasma-Seq follow-up CSPC4","Dataset Plasma-seq"],"category":["restricted"],"repository":["EGA"],"pubmed_abstract":["<h4>Background</h4>Patients with prostate cancer may present with metastatic or recurrent disease despite initial curative treatment. The propensity of metastatic prostate cancer to spread to the bone has limited repeated sampling of tumor deposits. Hence, considerably less is understood about this lethal metastatic disease, as it is not commonly studied. Here we explored whole-genome sequencing of plasma DNA to scan the tumor genomes of these patients non-invasively.<h4>Methods</h4>We wanted to make whole-genome analysis from plasma DNA amenable to clinical routine applications and developed an approach based on a benchtop high-throughput platform, that is, Illuminas MiSeq instrument. We performed whole-genome sequencing from plasma at a shallow sequencing depth to establish a genome-wide copy number profile of the tumor at low costs within 2 days. In parallel, we sequenced a panel of 55 high-interest genes and 38 introns with frequent fusion breakpoints such as the TMPRSS2-ERG fusion with high coverage. After intensive testing of our approach with samples from 25 individuals without cancer we analyzed 13 plasma samples derived from five patients with castration resistant (CRPC) and four patients with castration sensitive prostate cancer (CSPC).<h4>Results</h4>The genome-wide profiling in the plasma of our patients revealed multiple copy number aberrations including those previously reported in prostate tumors, such as losses in 8p and gains in 8q. High-level copy number gains in the AR locus were observed in patients with CRPC but not with CSPC disease. We identified the TMPRSS2-ERG rearrangement associated 3-Mbp deletion on chromosome 21 and found corresponding fusion plasma fragments in these cases. In an index case multiregional sequencing of the primary tumor identified different copy number changes in each sector, suggesting multifocal disease. Our plasma analyses of this index case, performed 13 years after resection of the primary tumor, revealed novel chromosomal rearrangements, which were stable in serial plasma analyses over a 9-month period, which is consistent with the presence of one metastatic clone.<h4>Conclusions</h4>The genomic landscape of prostate cancer can be established by non-invasive means from plasma DNA. Our approach provides specific genomic signatures within 2 days which may therefore serve as 'liquid biopsy'."],"pubmed_title":["Tumor-associated copy number changes in the circulation of patients with prostate cancer identified through whole-genome sequencing."],"pubmed_authors":["Heitzer Ellen E, Ulz Peter P, Belic Jelena J, Gutschi Stefan S, Quehenberger Franz F, Fischereder Katja K, Benezeder Theresa T, Auer Martina M, Pischler Carina C, Mannweiler Sebastian S, Pichler Martin M, Eisner Florian F, Haeusler Martin M, Riethdorf Sabine S, Pantel Klaus K, Samonigg Hellmut H, Hoefler Gerald G, Augustin Herbert H, Geigl Jochen B JB, Speicher Michael R MR"],"name_synonyms":["Plasma, Fresh, Frozen Plasmas, Fresh Frozen Plasmas, Fresh Frozen, Blood Plasma, metastatic prostate cancer., Frozen Plasma, metastatic prostate carcinoma, Fresh Frozen Plasma, Patient, Clients, Blood Plasmas, Blood, portion of plasma, prostate cancer metastatic, Plasmas, plasma, Client, prostate carcinoma metastatic"],"description_synonyms":["Fresh, other disease, DNS, Fresh Frozen Plasma, (Deoxyribonucleotide)n, determination, MBP-C, Neoplasms, Blood, R75289, instrument configuration, Benign Neoplasm, number, p55, MBP1, broad, Tumor, Malignant, presence, Deoxyribonucleic acids, metastatic prostate cancer, hardware, COLEC1, low depth, Deoxyribonucleic Acid, diseases, Core Genome, disease or disorder, diseases and disorders, Low, Chromosome 21, HSMBPC, Eosinophil granule major basic protein, metastatic., study, Fresh Frozen Plasmas, Fresh Frozen, Blood Plasma, erg-3, thymus nucleic acid, me75, human disease, metastatic prostate carcinoma, Malignancy, Genomes, Accessory Genome, Double Stranded, HardwareType, Proteoglycan 2, Deoxyribonucleic acid, MBL, erg_A, Myelin membrane encephalitogenic protein, MBP, SCAN, erg, D17Mit170, T1, non-neoplastic, Neoplasias, Clients, Blood Plasmas, MiSeq, D030036I24Rik, MBPD, Pregnancy-associated major basic protein, disorder, Homo sapiens disease, Malignancies, Double-Stranded DNA, (Deoxyribonucleotide)m, deoxyribonucleic acids, DNAn, associated, shallow, plasma, prostate carcinoma metastatic, Cancer, Tumors, Prostates, Frozen Plasma, Malignant Neoplasm, wide/broad, cou, DNAn+1, disorders, prostate cancer metastatic, medical condition, Double-Stranded, Tl3, Plasmas, Tl2, Client, Pangenome, BMPG, (Deoxyribonucleotide)n+m, Frozen Plasmas, Menstruation, count in organism, mld, Lr, Benign, Period, male prostate, C76307, chemical analysis, Diseases, Neoplasm, condition, MBL2D, shi, Hmbpr, ds-DNA, desoxyribose nucleic acid, Plasma, instrument, Benign Neoplasms, portion of plasma, EMBP, Cancers, whole genome, golli-mbp, Malignant Neoplasms, disease, wide, Pan-genome, Patient, DEL, Indexes, ds DNA, cardinality, Desoxyribonukleinsaeure, Bra, assay, Myelin A1 protein, DNA, other neoplasm, prostate, Neoplasia, prostata"],"pubmed_title_synonyms":["hereditary prostate cancer, cancer of the prostate, Malignant Neoplasm, Malignancy, Prostate Neoplasms, Neoplasms, Benign Neoplasm, number, familial, Benign Neoplasms, Cancers, whole genome, Tumor, Malignant, cancer of prostate, presence, Client, Prostate Neoplasm, Malignant Neoplasms, Neoplasias, count in organism, Prostatic Neoplasm, Benign, Cancer of the Prostate, Patient, Clients, cardinality, Prostatic Cancer, Neoplasm, Prostatic Cancers, Prostatic, prostate cancer, PC, NOS, Malignancies, associated, other neoplasm, Cancer of Prostate, Prostate Cancer, Neoplasia, Prostate, Cancer, Tumors, Prostate Cancers, Genomes."],"pubmed_abstract_synonyms":["Bones and Bone Tissue, Materials, Extranodal, insensitive, determination, MBP-C, Blood, instrument configuration, MBP1, Tumor, metastatic prostate cancer, osteogenic tissue, Liquid Biopsies, Techniques, low depth, sampling, Bone and Bone, diseases, primary tumour, Tumor Deposits, Method, diseases and disorders, Gonadectomies, Bone Tissues, treatment, HSMBPC, Eosinophil granule major basic protein, Fresh Frozen Plasmas, Fresh Frozen, human disease, thymus nucleic acid, me75, metastatic prostate carcinoma, Biopsies, Genomes, Extranodal Tumor Deposits, Tissue, HardwareType, procedures, Myelin membrane encephalitogenic protein, SCAN, D17Mit170, T1, allergic reaction, Prostatic Neoplasm, high frequency, Cancer of the Prostate, Methodological Studies, malignant neoplasm, MBPD, disease management, Therapies, Pregnancy-associated major basic protein, Condyles, Homo sapiens disease, Double-Stranded DNA, Malignancies, Biopsy, deoxyribonucleic acids, DNAn, associated, Bony Apophyses, shallow, plasma, prostate carcinoma metastatic, Tumors, Therapy, cancer of the prostate, Prostates, Frozen Plasma, wide/broad, Intervening Sequences, familial, Double-Stranded, Procedure, Tl3, Plasmas, Tl2, results, (Deoxyribonucleotide)n+m, Menstruation, mld, metastatic disease, Benign, C76307, Diseases, Genetic Materials, NOS, shi, Hmbpr, desoxyribose nucleic acid, Genetic Material, Tumor Deposit, resistant, instrument, portion of bone tissue, Benign Neoplasms, EMBP, whole genome, Methodological, Condyle, cancer of prostate, Methodological Study, Treatments, Intervening, Malignant Neoplasms, disease, metastatic, wide, Bony, Patient, bone, Material, primary tumor, metastatic tumor, ds DNA, Liquid, Cistron, Myelin A1 protein, Bony Apophysis, DNA, other neoplasm, prostate, Bone, Prostate, prostata, Fresh, other disease, DNS, Fresh Frozen Plasma, Procedures, Prostate Neoplasms, (Deoxyribonucleotide)n, Neoplasms, R75289, Benign Neoplasm, number, p55, Gene, Extracapsular Extension, broad, Malignant, presence, Deoxyribonucleic acids, hardware, COLEC1, Deoxyribonucleic Acid, sensitive, Core Genome, Prostatic Cancers, Studies, disease or disorder, Extranodal Tumor Deposit, Low, Chromosome 21, Cancer of Prostate, Technique, sensitivity, Prostate Cancers, Blood Plasma, erg-3, Genetic, Malignancy, Tissues, Accessory Genome, Double Stranded, Proteoglycan 2, Deoxyribonucleic acid, MBL, erg_A, MBP, erg, non-neoplastic, Neoplasias, Study, Clients, Blood Plasmas, MiSeq, D030036I24Rik, Prostatic, disorder, Apophysis, Intron, (Deoxyribonucleotide)m, Cancer, hereditary prostate cancer, Apophyses, Malignant Neoplasm, cou, DNAn+1, disorders, medical condition, prostate cancer metastatic, Cistrons, Client, Pangenome, BMPG, metastatic neoplasm, Bones and Bone, Frozen Plasmas, Sequences, count in organism, Intervening Sequence, Lr, MT, Liquid., Period, Sequence, male prostate, Prostatic Cancer, chemical analysis, Neoplasm, condition, MBL2D, background, bones, techniques, ds-DNA, Gonadectomy, Plasma, Castrations, osseous tissue, primary cancer, frequent, primary neoplasia, portion of plasma, Cancers, Bones, golli-mbp, malignant tumor, introduction, Prostate Neoplasm, sample collection, mineralized bone tissue, Pan-genome, Therapeutic, Bone Tissue, DEL, Indexes, cardinality, metastatic tumour, Desoxyribonukleinsaeure, Bra, prostate cancer, PC, Treatment, calcium tissue, assay, bone organ, Prostate Cancer, Neoplasia, methodology"],"additional_accession":[]},"is_claimable":false,"name":"Plasma-Seq of patients with metastatic prostate cancer","description":"Study 1 In this study we analysed patients with metastatic prostate cancer to scan their tumor genomes noninvasively in plasma DNA. We wanted to make whole-genome analysis from plasma DNA amenable to clinical routine applications and developed an approach based on a benchtop high-throughput platform, i.e. Illuminas MiSeq instrument. We performed whole-genome sequencing from plasma at a shallow sequencing depth to establish a genome-wide copy number profile of the tumor at low costs within 2 days. The genome-wide profiling in the plasma of our patients revealed multiple copy number aberrations including those previously reported in prostate tumors, such as losses in 8p and gains in 8q. High-level copy number gains in the AR locus were observed in patients with CRPC but not with CSPC disease. We identified the TMPRSS2-ERG rearrangement associated 3-Mbp deletion on chromosome 21 and found corresponding fusion plasma fragments in these cases. In an index case multiregional sequencing of the primary tumor identified different copy number changes in each sector, suggesting multifocal disease. Our plasma analyses of this index case, performed 13 years after resection of the primary tumor, revealed novel chromosomal rearrangements, which were stable in serial plasma analyses over a 9 months period, which is consistent with the presence of one metastatic clone.  Our approach provides specific genomic signatures within 2 days which may therefore serve as “liquid biopsy”.","dates":{"updated":"2019-10-31 12:52:09"},"accession":"EGAS00001000451","cross_references":{"TAXONOMY":["9606"],"pubmed":["23561577"],"EGA":["EGAD00001000396","EGAD00001000364","EGAC00001000072"]}}