{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"dataset_type":["Affymetrix_U133plus2-"],"full_dataset_link":["https://ega-archive.org/datasets/EGAD00010000502"],"sample_count":["35"],"description":["EGA dataset EGAD00010000502"],"repository":["EGA"],"title":["Title not provided"],"pubmed_abstract":["High-grade serous ovarian cancer (HGSC) is characterized by poor outcome, often attributed to the emergence of treatment-resistant subclones. We sought to measure the degree of genomic diversity within primary, untreated HGSCs to examine the natural state of tumour evolution prior to therapy. We performed exome sequencing, copy number analysis, targeted amplicon deep sequencing and gene expression profiling on 31 spatially and temporally separated HGSC tumour specimens (six patients), including ovarian masses, distant metastases and fallopian tube lesions. We found widespread intratumoural variation in mutation, copy number and gene expression profiles, with key driver alterations in genes present in only a subset of samples (eg PIK3CA, CTNNB1, NF1). On average, only 51.5% of mutations were present in every sample of a given case (range 10.2-91.4%), with TP53 as the only somatic mutation consistently present in all samples. Complex segmental aneuploidies, such as whole-genome doubling, were present in a subset of samples from the same individual, with divergent copy number changes segregating independently of point mutation acquisition. Reconstruction of evolutionary histories showed one patient with mixed HGSC and endometrioid histology, with common aetiologic origin in the fallopian tube and subsequent selection of different driver mutations in the histologically distinct samples. In this patient, we observed mixed cell populations in the early fallopian tube lesion, indicating that diversity arises at early stages of tumourigenesis. Our results revealed that HGSCs exhibit highly individual evolutionary trajectories and diverse genomic tapestries prior to therapy, exposing an essential biological characteristic to inform future design of personalized therapeutic solutions and investigation of drug-resistance mechanisms."],"pubmed_title":["Distinct evolutionary trajectories of primary high-grade serous ovarian cancers revealed through spatial mutational profiling."],"pubmed_authors":["Bashashati Ali A, Ha Gavin G, Tone Alicia A, Ding Jiarui J, Prentice Leah M LM, Roth Andrew A, Rosner Jamie J, Shumansky Karey K, Kalloger Steve S, Senz Janine J, Yang Winnie W, McConechy Melissa M, Melnyk Nataliya N, Anglesio Michael M, Luk Margaret T Y MT, Tse Kane K, Zeng Thomas T, Moore Richard R, Zhao Yongjun Y, Marra Marco A MA, Gilks Blake B, Yip Stephen S, Huntsman David G DG, McAlpine Jessica N JN, Shah Sohrab P SP"],"name_synonyms":["Data Set."],"pubmed_title_synonyms":["distinct."],"pubmed_abstract_synonyms":["Materials, insensitive, degree (angle), Product, determination, selection process, Mammalian, Salpinx, PI3K, histology, Tp53, Mutations, Transcript Expression Analysis, p110-alpha, DmelCG8318, dmTAF[[II]]230, Mesc, type I, bbl, Pharmaceutical Product, Gene Expression Monitorings, p110alpha, Whole Transcriptome, Transcriptome Sequencing, Analysis, Profilings, Catnb, Fs(3)Hor, anatomy and histology, peripheral type, treatment, average, Divorced, DmelCG2684, ctnnb1, Gene Expressions, E030030H24Rik, TFIID TAF250, Analyses, BCC7, Genomes, cel, Complete Exome Sequencing, Whole Transcriptome Sequencing, type 1 neurofibromatosis, Divorces, NTef2, MCAP, Salpinges, Gene Expression Analysis, oviducts, medicine, Pharmaceutical, sample, disease management, Oviducts, Therapies, MCMTC, Bfc, Therapy, Tube, dTAF[[II]]230, female paramesonephric duct, Exome, CG8318, Monitorings, TAF200, armadillo, Tubes, TAFII-250, TAF250/230, Uterine, results, Fs(3)Sz11, beta-catenin, Gene Expression, TAFII250, Recklinghausen's disease, Genetic Materials, bfy, Pharmaceutic, dNF1, Genetic Material, Complete Transcriptome, resistance., histopathology, resistant, Transcriptome Profilings, common, paramesonephric duct of female, whole genome, CG17603, TAF[[II]], Treatments, early, Fallopian, Gene Expression Analyses, Patient, Taf250, Material, SR3-5, Horka, Whole Exome Sequencing, P53, CG2684, p44, Fs(3)Horka, bhy, Cistron, Expression Analysis, WSS, other neoplasm, Transcriptome Sequencings, TAF230, d230, Mammalian Oviduct, Complete Exome, Fallopian tube, Uterine Tube, p53, number, Gene, tuba uterina, dTAFII250, neurofibromatosis, PRO2286, LFS1, EfW1, presence, Gene Expression Profilings, morphology, mRNA Differential Displays, Gene Expression Pattern Analysis, dmTAF1, Taf230, Uterine Salpinx, DmF2, ctnnb, Separated, TAF250, lod, Drugs, study, WES, Taf200, anatomy, Complete, Exome Sequencings, dTAF[[II]]250, Genetic, cell, Mammalian Oviducts, Fallopian Tube, Transcriptomics, Taf1p, Transcript Expression, Transcriptome Analysis, Nf-1, NFNS, Oviduct, Expressions, VRNF, Sequencing, Monitoring, Solution, dTAF250, Whole Exome, Trp53, drugs, OK/SW-cl.35, Clients, Whole, malignant ovarian serous tumour, Expression, MCM, TRP53, Preparation, fallopian tubes, serous ovarian cancer, Expression Analyses, salpinx, NF1, NF-1, nf1, TAF, von Reklinghausen disease, Uterine Salpinges, Pharmaceuticals, Products, Profiling, TAF[[II]]250, Transcriptome, Complete Exome Sequencings, 6330412C24Rik, drug, p110, Point Mutations, l(3)84Ab, BG:DS00004.13, Cistrons, Client, Cell, Xp53, dTAF230, Differential Display, transcription profiling, neurofibromatosis type 1 microdeletion syndrome, Exome Sequencing, count in organism, Transcript Expression Analyses, CTNNB, CWS5, p230, chemical analysis, uterine tube, TAF[[II]]250/230, TFIID, salpinges, mRNA Differential Display, Mutation, gene expression profiling, tuba uterinae, Taf[[II]]250, Gene Expression Monitoring, Separation, mammalian oviduct, MRD19, Complete Transcriptome Sequencing, TAF[[II]]230, Exhibit, Transcriptome Profiling, distinct, mRNA, Pharmaceutic Preparations, Separations, Von Recklinghausen disease, fallopian tube, uterine tube (sensu Mammalia), patient, TAF[II]250, arc degree, Differential Displays, Lds, Transcriptome Analyses, sample population, Drug, caPI3K, Preparations, CLOVE, DmelCG17603, Therapeutic, Uterine Tubes, Point, cardinality, AW494271, Treatment, assay, Pharmaceutical Products, Pharmaceutical Preparation, TAF1"],"additional_accession":[]},"is_claimable":false,"name":"SNP6_dataset_case - samples","description":"Case samples using SNP Array 6.0","dates":{"updated":"2017-07-26 15:39:25"},"accession":"EGAD00010000502","cross_references":{"TAXONOMY":["9606"],"pubmed":["23780408"],"EGA":["EGAC00000000011","EGAS00001000547"]}}