{"database":"EGA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"technology_type":["Illumina HiSeq 2000"],"study_type":["Whole Genome Sequencing"],"full_dataset_link":["https://ega-archive.org/studies/EGAS00001000484"],"host":["EGA"],"description":["EGA study EGAS00001000484"],"dataset_title":["Sporadic Parathyroid Carcinoma"],"repository":["EGA"],"category":["restricted"],"name_synonyms":["carcinoma of parathyroid, Transcriptome, determination, Transcriptome Profile, carcinoma of parathyroid gland, Profile, Expression Profiles, Gene Expression Profile, Gene, PRTC, adenocarcinoma of parathyroid, carcinoma of the parathyroid gland, adenocarcinoma of parathyroid gland, parathyroid adenocarcinoma., whole genome, Profiles, parathyroid gland adenocarcinoma, parathyroid gland cancer, Signatures, malignant neoplasm of parathyroid gland, Gene Expression, parathyroid neoplasm, malignant neoplasm of the parathyroid, carcinoma of the parathyroid, Expression Signature, Gene Expression Profiles, parathyroid gland carcinoma, Expression Signatures, Gene Expression Signatures, chemical analysis, parathyroid carcinoma, Transcriptomes, parathyroid cancer, Gene Expression Signature, assay, Signature, cancer of parathyroid gland, adenocarcinoma of the parathyroid gland, parathyroid gland neoplasm, cancer of the parathyroid gland, Expression Profile, adenocarcinoma of the parathyroid, Transcriptome Profiles"],"description_synonyms":["type 1, 2610315D21Rik, parathyroid adenoma with cystic changes, Materials, tumor suppressor, 2410041A17Rik, Supportive Care, Incidences, MTC1, cD1, Person-time Rates, BC058659, Proportion, Parathyroid Hormone (1-34), fs(1)M34, Progress Reports, Tumor, sialic acid-binding Ig-like lectin 5, Parathyroid Hormone Peptide (1-34), parathyroid adenomatosis, beta-cat, DmTOR, BC032281, DmelCG12051, Mutations, p110-alpha, hyperparathyroidism 2, cell cycle regulator, Reto, Summary Report, Siglec5, HEL-176, CG4601, RAFT1, Mammalian target of rapamycin, Parathyrin, hyperparathyroidism-jaw tumor syndrome, beta-Cat, A, calcio, C, cyt5C, C77269, DHO, Progress Report, catabolism, D-ret, CycD1, Basen, CG18572, Bodily, malignant neoplasm of the parathyroid gland, Dm Arm, C81219, endocrine, Upper, MCAP, Secretion, Field Reports, Secretions, Role Concepts, ccnd1a, ACT, Homo sapiens disease, Act, Nucleotide, Siglece, Blood Coagulation Factor IV, Ca, Tumors, RET, KABUK1, carcinoma of parathyroid, B230333E16Rik, Coagulation, Actin/BAP47, CTE-II, AACT, familial, CTE-IIa, act, Ach1, hBACH, ACH1, carcinoma of the parathyroid gland, not genetically inherited, malignant neoplasm of parathyroid gland, act42A, ret, exocrine gland fluid/secretion, GIG25, Bodily Secretion, Incidence Rates, KU-MEL-1, Benign, Role Concept, HSCR1, Su(b), Recrudescence, AFFX-Dros-ACTIN_M_r_at, GIG24, parathyroid carcinoma, DmelCG14396, Base2, Base1, Role, actin, secretion, Person-time Rate, LACH, nucleotides, Cares, DmelCG4027, death rate, Rapamycin and FKBP12 target 1, Field, Benign Neoplasms, INSDC_feature:gene, parathyroid gland adenocarcinoma, EG:86E4.6, surveillance, INK4c, Parathyroid, Malignant Neoplasms, INK4d, actin5C, Report, parathormone, multiple, Brachiums, Material, betacat, malignant parathyroid gland tumor, Supportive, School-Age Population, Hypercalcaemia, Secondary Attack Rates, other neoplasm, exocrine gland secretion, BACH, INK4C, parathyroid adenocarcinoma, HPT-JT, l(1)Ab, Act5c, HD-59, malignant tumor of the parathyroid, hyperparathyroidism, carcinoma of parathyroid gland, Neoplasms, SLG, ACT5C, Surgery, MEN2, Bach, MLL1B, MEN1, Hormone, parathyrin, Rate, CG1061, FIHP, Factor IV, disease or disorder, parathyroid cancer, DmHD-59, Cell growth-inhibiting gene 24|25 protein, TOR, Attack Rates, parathyroid gland neoplasm, Upper Arm, Ca(0), School-Age Populations, HRX2, p18-INK4C, KMT2B, familial cystic, Bx34, occurrence, Recrudescences, BRWS2, prevalence, Cyl-1, study., malignant tumor of the parathyroid gland, tor, Tpr, TPR, Population, fs(1)829, Neoplasias, Cumulative, anon-EST:fe2D2, parathyroid neoplasm, malignant neoplasm of the parathyroid, HYX, Hrpt2, bodily secretion, parathyroid, DmelCG18572, Person-time, Syndrome, Person time Rate, prad1, T11, Supportive Cares, MCM, adenocarcinoma of the parathyroid gland, Investigative Reports, siglec-5, cancer of the parathyroid gland, constitutitional genetic, HRPT2, BCL1, Frap1, ccnd1, Act-5C, HRPT1, Cancer, disease remission, 2610014H22Rik, 42A, CPS, ALR, Malignant Neoplasm, UNQ9215/PRO34042, degradation, disorders, dJ393D12.2, Point Mutations, Secondary Attack, FRAP1, FRAP2, mTOR, AMH, Milk-Alkali, DRet, DRET, c-Ret, Concept, l(1)arm, Cumulative Incidences, endocrine adenomatosis, MT, Arms, malignant parathyroid neoplasm, CWS5, beta-actin, C130030P16Rik, Research Reports, chemical analysis, M32055, Neoplasm, hyperparathyroidism-2, condition, Act42, dRET, dRet, CDHF12, outbreaks, Mutation, Calcium, primary cancer, PYR1, Cancers, FRAP, WBP7, Wbp7, School Age Populations, malignant tumor, Parathyroid Hormone (1-84), upper extremity, CG11579, caPI3K, Incidence Proportion, mKIAA0304, CLOVE, PTH(1-34), CT16317, Reports, Point, MTOR, DRORUD, epidemics, BAP47, High blood calcium levels, ACTSG, nucleobases, parathyroid secreting cell, hereditary, Bap47, Neoplasia, Dret, TRX2, biochemical pathways, l(1)G0410, Palliative Treatment, beta-cat-arm, determination, ACTG, ACTE, Blood, Calcium 40, FKBP12-rapamycin complex-associated protein, endocrine adenomatosis multiple, PI3K, Serum, l(2)k03905, csp2, Act5, l(1)G0420, Natpara, School-Age, CG13778, diseases, Roles, MIF, malignant parathyroid gland neoplasm, Concepts, diseases and disorders, p110alpha, Incidence Rate, Relapses, Palliative, MIS, Summary Reports, ARM, Arm, hyperparathyroidism type 2, human disease, PTH (1-84), CAGL114, long, Recurrences, bases, adenocarcinoma of parathyroid, Estimated, dtor, arm, genetic, Progress, TNRC21, malignant neoplasm, act 42A, Ac5C, CG4027, biotransformation, Malignancies, RET51, MCMTC, dTOR, dTor, CG33266, FK506-binding protein 12-rapamycin complex-associated protein 1, Therapy, Mechanistic target of rapamycin, Relapse, Upper Arms, l(1)G0330, PLATEST, HPTJT, Nucleobase, external secretion, frequency, 8430414L16Rik, familial primary hyperparathyroidism with multiple ossifying jaw fibromas, p18, beta-catenin/Arm, Blood Serum, LACH1, 9330151F09Rik, shortened, CDHR16, with multiple ossifying jaw fibromas, Investigative Report, Alpha-1-antichymotrypsin His-Pro-less, School Age, Diseases, DFNA26, Genetic Materials, GAT, DFNA20, bcl-1, Genetic Material, RAPT1, PTC, l(1)G0234, Populations, PTH, l(1)G0117, Actin, mnn1, MEN2A, MEN2B, morbidity, Treatments, beta-actin/Bap47, l(1)G0486, loss of, NS21, l(1)G0245, calcium, disease, C430014K11Rik, Palliative Supportive Care, l(1)G0009, Patient, ACTL3, t12687 ALR Dm, C1orf28, Lach1, 5092, Base, ALDR1, hypercalcemia, Parathormone, AAD10, Cistron, p18INK4c, inherited genetic, DmelCG11579, short, Platelets, base, Milk-Alkali Syndrome, other disease, l(1)G0010, exocrine gland fluid, Palliative Therapy, exocrine gland fluid or secretion, Increased calcium in blood, CG5092, TRAP150, Benign Neoplasm, CG12051, Gene, BC027756, Serpin A3, Malignant, l(2)k17004, Menin1, RET-ELE1, Hypercalcemias, Secondary Attack Rate, l(1)G0025, familial primary, MEA 1, Investigative, brachium, 20Ca, Care, KMS, Anti-Muellerian hormone, hyperparathyroidism 2 with jaw tumors, DmelCG13778, Milk Alkali Syndrome, malignant neoplasm of parathyroid, Palliative Treatments, SCG2, DmelCG8274, Calcium-40, hormones, act5C, Genetic, Malignancy, epithelial body, stubby, multiple endocrine neoplasia, menin, adenocarcinoma of parathyroid gland, flat, Brachium, malignant tumor of parathyroid, parathyroid gland cancer, non-neoplastic, MLL2, Mll2, Act42a, secreted substance, MLL4, Mll4, 1700027G07Rik, time of survival, parathyroid gland carcinoma, Clients, disorder, AW045611, Incidence Proportions, cancer of parathyroid gland, School Age Population, CT24817, l(1)2Bv, adenocarcinoma of the parathyroid, Cte-II, incidence, l(1)G0177, Trap150, D11S287E, 6330412C24Rik, malignant parathyroid tumor, Attack Rate, Cumulative Incidence, Incidence, p110, medical condition, Kalzium, FRAP/TOR, Muellerian-inhibiting substance, Cistrons, DmelCG5092, Client, CG14396, HEL-S-6, PRAD1, SIGLECL1, 2.7.11.1, WBP-7, survival, CAD, carcinoma of the parathyroid, Chromosome 1, U21B31, MEN1 somatic mutations, Can, AI327039, DD3, rare (European definition), ACTA3, l(1)G0079, biodegradation, VSCM, hereditary hyperparathyroidism-jaw tumor syndrome, act 5C, PRTC, CT24745, Rapamycin target protein 1, AI327068, patient, l(1)G0192, endemics, Secondary, MEAI, Coagulation Factor IV, Attack, CG8274, Treatment, assay, Palliative Surgery, Summary, Serums, Actin5C, Field Report, RET9"],"additional_accession":[]},"is_claimable":false,"name":"Whole genome and transcriptome analysis of a sporadic and recurring parathyroid carcinoma","description":"Parathyroid carcinoma is an extremely rare endocrine malignancy with an estimated incidence of less than 1 per million population. Excessive secretion of parathyroid hormone, extremely high serum calcium level and the deleterious effects of hypercalcemia are the clinical manifestations of the disease. Up to 60% of patients develop multiple disease recurrences and although long-term survival is possible with palliative surgery, permanent remission is rarely achieved. Molecular drivers of sporadic parathyroid carcinoma have remained largely unknown. Previous studies, mostly based on familial cases of the disease, suggested a potential role for the tumor suppressor MEN1 and proto-oncogene RET in benign parathyroid tumorigenesis while the tumor suppressor HRPT2 and proto-oncogene CCND1 may also act as drivers in parathyroid cancer. Here, we report the complete genomic analysis of a sporadic and recurring parathyroid carcinoma. Mutational landscapes of the primary and recurrent tumor specimens were analyzed using high throughput sequencing technologies. Such molecular profiling allowed for identification of somatic mutations never previously identified in this malignancy. These included single nucleotide point mutations in well characterized cancer genes such as mTOR, MLL2, CDKN2C and PIK3CA. Comparison of acquired mutations in patient-matched primary and recurrent tumors revealed loss of PIK3CA activating mutation during the evolution of the tumor from the primary to the recurrence. Structural variations leading to gene fusions and regions of copy loss and gain were identified at a single-base resolution. Loss of short arm of chromosome 1 along with somatic mis-sense and truncating mutations in CDKN2C and THRAP3, respectively, provide new evidence for the potential role of these genes as tumor suppressors in parathyroid cancer. The key somatic mutations indentified in this study can serve as novel diagnostic markers as well as therapeutic targets.","dates":{"updated":"2017-07-26 15:39:25"},"accession":"EGAS00001000484","cross_references":{"TAXONOMY":["9606"],"EGA":["EGAD00001000370","EGAC00000000011"]}}