{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"technology_type":["Complete Genomics (COMPLETE_GENOMICS)"],"study_type":["Other"],"full_dataset_link":["https://ega-archive.org/studies/EGAS00001001909"],"host":["EGA"],"description":["EGA study EGAS00001001909"],"dataset_title":["Premalignant SOX2 in ovarian cancer patients"],"repository":["EGA"],"category":["restricted"],"pubmed_abstract":["Current screening methods for ovarian cancer can only detect advanced disease. Earlier detection has proved difficult because the molecular precursors involved in the natural history of the disease are unknown. To identify early driver mutations in ovarian cancer cells, we used dense whole genome sequencing of micrometastases and microscopic residual disease collected at three time points over three years from a single patient during treatment for high-grade serous ovarian cancer (HGSOC). The functional and clinical significance of the identified mutations was examined using a combination of population-based whole genome sequencing, targeted deep sequencing, multi-center analysis of protein expression, loss of function experiments in an in-vivo reporter assay and mammalian models, and gain of function experiments in primary cultured fallopian tube epithelial (FTE) cells. We identified frequent mutations involving a 40kb distal repressor region for the key stem cell differentiation gene SOX2. In the apparently normal FTE, the region was also mutated. This was associated with a profound increase in SOX2 expression (p<2(-16)), which was not found in patients without cancer (n=108). Importantly, we show that SOX2 overexpression in FTE is nearly ubiquitous in patients with HGSOCs (n=100), and common in BRCA1-BRCA2 mutation carriers (n=71) who underwent prophylactic salpingo-oophorectomy. We propose that the finding of SOX2 overexpression in FTE could be exploited to develop biomarkers for detecting disease at a premalignant stage, which would reduce mortality from this devastating disease."],"pubmed_title":["Premalignant SOX2 overexpression in the fallopian tubes of ovarian cancer patients: Discovery and validation studies."],"pubmed_authors":["Hellner Karin K, Miranda Fabrizio F, Fotso Chedom Donatien D, Herrero-Gonzalez Sandra S, Hayden Daniel M DM, Tearle Rick R, Artibani Mara M, Carrami Eli M EM, Williams Ruth R, Gaitskell Kezia K, Elorbany Samar S, Xu Ruoyan R, Laios Alex A, Buiga Petronela P, Ahmed Karim K, Dhar Sunanda S, Zhang Rebecca Yu RY, Campo Leticia L, Myers Kevin A KA, Lozano María M, Ruiz-Miró María M, Gatius Sónia S, Mota Alba A, Moreno-Bueno Gema G, Matias-Guiu Xavier X, Benítez Javier J, Witty Lorna L, McVean Gil G, Leedham Simon S, Tomlinson Ian I, Drmanac Radoje R, Cazier Jean-Baptiste JB, Klein Robert R, Dunne Kevin K, Bast Robert C RC, Kennedy Stephen H SH, Hassan Bassim B, Lise Stefano S, Garcia María José MJ, Peters Brock A BA, Yau Christopher C, Sauka-Spengler Tatjana T, Ahmed Ahmed Ashour AA"],"name_synonyms":["Ovary Cancer, RGD1565646, Tube, Cancer of Ovary, Mammalian Oviduct, ysb, ovarian neoplasm, Uterine Tube, female paramesonephric duct, Neoplasms, Mammalian, Salpinx, Ovary, SRY-box2, tuba uterina, Tubes, Ovary Cancers, Uterine, Client, ANOP3, malignant tumour of ovary, ovarian cancer, epithelial, Ovarian, Uterine Salpinx, malignant Ovarian tumor, anop3, Neoplasm, salpinges, Ovary Neoplasm, Validation Studies., Cancer of the Ovary, mammalian oviduct, sox-2, MCOPS3, lcc, Mammalian Oviducts, Ovarian Cancer, Fallopian Tube, ovarian epithelial cancer, OC, uterine tube (sensu Mammalia), paramesonephric duct of female, Ovary Neoplasms, Cancers, Xsox-2, Oviduct, primary ovarian cancer, ovary neoplasm, Fallopian, Salpinges, Sox-2, Ovarian Neoplasm, Patient, Uterine Tubes, tumor of the Ovary, Clients, Oviducts, mcops3, Ovarian Cancers, fallopian tubes, salpinx, Uterine Salpinges, Cancer"],"description_synonyms":["Ovary Cancer, other disease, Laser Capture, Microdissection, Capture Microdissections, Effects, chemotherapy, Neoplasms, Benign Neoplasm, pharmacotherapy, Pharmacotherapies, Tumor, Malignant, Long Term, temporal, Chemotherapies, Mutations, malignant tumour of ovary, ovarian cancer, diseases, Ovarian, Microdissections, disease or disorder, diseases and disorders, DmF2, Relapses, Fs(3)Hor, Effect, Drug Therapies, lod, treatment, study, DmelCG2684, human disease, Complete, Whole Genome, Malignancy, Longterm, Recrudescences, long, Recurrences, Ovarian Cancer, Complete Genome Sequencing, Long-Term, NTef2, primary ovarian cancer, Sequencing, non-neoplastic, Neoplasias, 10^[-6], laser-assisted microdissection, malignant neoplasm, Clients, Whole, heterogeneity, disease management, Therapies, disorder, Homo sapiens disease, malignant ovarian serous tumour, Long-Term Effect, Malignancies, Ovarian Cancers, serous ovarian cancer, Long-Term Effects, Capture Microdissection, incidence, Cancer, Tumors, Therapy, Relapse, Cancer of Ovary, Malignant Neoplasm, ovarian neoplasm, Ovary, disorders, Genome Sequencing, Longterm Effect, medical condition, Ovary Cancers, Client, Cell, Fs(3)Sz11, read, Complete Genome, MT, Benign, epithelial, Recrudescence, malignant Ovarian tumor, Long Term Effects, Diseases, Neoplasm, Laser Capture Microdissections, condition, Chemotherapy, LCM, Ovary Neoplasm, Cancer of the Ovary, Epistemology, primary cancer, Pharmacotherapy, ovarian epithelial cancer, OC, Benign Neoplasms, Ovary Neoplasms, patient, Cancers, Lds, Treatments, malignant tumor, early, ovary neoplasm, Longterm Effects, Drug, LMD, disease, Ovarian Neoplasm, Patient, Therapeutic, Horka, tumor of the Ovary, CG2684, Fs(3)Horka, Treatment, pharmacologic therapy, Laser, other neoplasm, Neoplasia, Malignant Neoplasms."],"pubmed_title_synonyms":["Ovary Cancer, RGD1565646, Tube, Cancer of Ovary, Mammalian Oviduct, ysb, ovarian neoplasm, Uterine Tube, female paramesonephric duct, Neoplasms, Mammalian, Salpinx, Ovary, SRY-box2, tuba uterina, Tubes, Ovary Cancers, Uterine, Client, ANOP3, malignant tumour of ovary, ovarian cancer, epithelial, Ovarian, Uterine Salpinx, malignant Ovarian tumor, anop3, Neoplasm, salpinges, Ovary Neoplasm, Validation Studies., Cancer of the Ovary, mammalian oviduct, sox-2, MCOPS3, lcc, Mammalian Oviducts, Ovarian Cancer, Fallopian Tube, ovarian epithelial cancer, OC, uterine tube (sensu Mammalia), paramesonephric duct of female, Ovary Neoplasms, Cancers, Xsox-2, Oviduct, primary ovarian cancer, ovary neoplasm, Fallopian, Salpinges, Sox-2, Ovarian Neoplasm, Patient, Uterine Tubes, tumor of the Ovary, Clients, Oviducts, mcops3, Ovarian Cancers, fallopian tubes, salpinx, Uterine Salpinges, Cancer"],"pubmed_abstract_synonyms":["Biological Markers, Viral Marker, Materials, Surrogate Endpoints, determination, Laboratory, History, Mammalian, Salpinx, DmelCG30169, Biochemical, Endpoint, protein, Tumor, Serum, PPP1R53, Long Term, Mutations, Case Fatality Rates, School-Age, Death Rates, Techniques, malignant tumour of ovary, Laboratory Markers, ovarian cancer, BcDNA:SD25109, diseases, Method, Biological, Familiar breast and Ovarian cancer syndrome, IRIS, diseases and disorders, Excess Mortalities, BROVCA1, BROVCA2, protein aggregate, Fs(3)Hor, Effect, treatment, average, human disease, DmelCG2684, FAD1, BRCC1, BRCC2, Crude Mortality Rates, Natural, PNCA4, procedures, NTef2, Xsox-2, primary ovarian cancer, PNCA2, Salpinges, geographical area, high frequency, Immune, Markers, Methodological Studies, oviducts, malignant neoplasm, scientific observation, Viral Markers, CFR Case Fatality Rate, disease management, Oviducts, Therapies, Homo sapiens disease, Malignancies, stage, Ovarian Cancers, Age-Specific Death Rate, Long-Term Effects, RAB163, FACD, Tumors, Diagnostic Findings, Therapy, hereditary breast ovarian cancer, SIGNS SYMPTOMS, Tube, Cancer of Ovary, Viral, ysb, Surrogate Endpoint, BRCA1, BRCA2, female paramesonephric duct, DESC, Genome Sequencing, Longterm Effect, Crude Death, BRCAI, Biochemical Markers, Procedure, Tubes, Biologic Marker, Uterine, ANOP3, CG13583, Fs(3)Sz11, CG13584, Crude Mortality, Mortality, Complete Genome, Benign, epithelial, Marker, School Age, malignant Ovarian tumor, Diseases, anop3, Genetic Materials, XRCC11, Genetic Material, Ovary Neoplasm, Populations, positional polypeptide feature, sox-2, End Points, death rate, Benign Neoplasms, common, Mortalities, Ovary Neoplasms, paramesonephric duct of female, INSDC_feature:gene, Methodological, Immunologic, Laboratory Marker, Methodological Study, Treatments, ovary neoplasm, early, brca2, Fallopian, Malignant Neoplasms, loss of, Fancd1, AI256696, disease, Sox-2, Mortality Rate, Crude Death Rate, FAD, Patient, Material, Biochemical Marker, Horka, CG2684, AW045498, Fs(3)Horka, Cistron, medical condition., School-Age Population, Mortality Determinant, Clinical Finding, RNF53, Ovary Cancer, RGD1565646, other disease, Mammalian Oviduct, Procedures, GLM3, Effects, region or site annotation, Clinical Markers, Fallopian tube, Uterine Tube, Clinical Marker, Mortality Declines, Neoplasms, developmental stage, Benign Neoplasm, Excess, Gene, tuba uterina, Crude Mortality Rate, protein-containing complex, Malignant, mortality measurement, CG30169, Symptoms and Signs, Surrogate End Points, Age-Specific Death, Mortality Determinants, Crude, Surrogate Markers, Rate, Determinant, Ovarian, Uterine Salpinx, Studies, Gene Products, disease or disorder, Case Fatality, DmF2, FANCD1, Finding, Technique, lod, School-Age Populations, Biomarker, Differential Mortality, positional, Complete, Excess Mortality, Whole Genome, Genetic, Clinical, Malignancy, Longterm, MCOPS3, Mammalian Oviducts, Biological Marker, Ovarian Cancer, Complete Genome Sequencing, Fallopian Tube, Long-Term, Population, Age-Specific, Oviduct, FANCS, Sequencing, non-neoplastic, Study, Neoplasias, Immunologic Markers, FANCB, Clients, Whole, FANCD, Mortality Rates, mortality rate, Crude Death Rates, disorder, malignant ovarian serous tumour, Long-Term Effect, School Age Population, fallopian tubes, serous ovarian cancer, salpinx, Immunologic Marker, Age Specific Death Rate, Biologic, Uterine Salpinges, Cancer, measuring, Malignant Neoplasm, Mortality Decline, ovarian neoplasm, protein complex, Proteins, Serum Markers, Ovary, disorders, SRY-box2, End Point, PSCP, medical condition, function, Ovary Cancers, Cistrons, Client, Cell, Immune Marker, Case Fatality Rate, Signs and Symptoms, MT, survival, native protein, Surrogate End Point, Long Term Effects, chemical analysis, Protein, Neoplasm, uterine tube, sequence, condition, Salpingo-oophorectomies, salpinges, techniques, Determinants, Death, epitheliocyte, tuba uterinae, Biologic Markers, Cancer of the Ovary, Rates, mammalian oviduct, Death Rate, primary cancer, Serum Marker, frequent, Surrogate, lcc, Endpoints, 30169, dmbrca2, ovarian epithelial cancer, OC, fallopian tube, uterine tube (sensu Mammalia), Salpingo oophorectomy, patient, Cancers, Age-Specific Death Rates, Lds, School Age Populations, malignant tumor, primary structure of sequence macromolecule, Surrogate Marker, Longterm Effects, Protein Gene Products, Gene Proteins, Differential, Ovarian Neoplasm, Therapeutic, tumor of the Ovary, Uterine Tubes, mcops3, Decline, Treatment, assay, Neoplasia, Differential Mortalities, methodology, Immune Markers"],"additional_accession":[]},"is_claimable":false,"name":"Premalignant SOX2 overexpression in the fallopian tubes of ovarian cancer patients: Discovery and validation studies","description":"To identify early driver mutations in ovarian cancer cells, we used dense whole genome sequencing of micrometastases and microscopic residual disease collected at three time points from a single patient during treatment for high-grade serous ovarian cancer (HGSOC). Laser capture microdissection of tumour islets was performed on samples prior to chemotherapy, after three cycles of chemotherapy and at recurrence. Long frament read whole genome sequencing was performed and mutations were identified. To our knowledge, this is the first longitudinal study that attempts to investigate spatial and temporal micro-heterogeneity in cancer.","dates":{"updated":"2017-07-26 15:39:29"},"accession":"EGAS00001001909","cross_references":{"TAXONOMY":["9606"],"pubmed":["27492892"],"EGA":["EGAD00001002734","EGAC00001000518"]}}