Paraneoplastic Secretion of Multiple Phosphatonins from a Deep Fibrous Histiocytoma Causing Oncogenic Osteomalacia
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PROVIDER: PRJNA673204 | ENA |
REPOSITORIES: ENA
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Project description:This data describes the first case of oncogenic osteomalacia due to a plexiform fibrohistiocytic tumor which coincidentally has been found for the first time to induce profound muscle weakness via the overexpression of three phosphatonins which resolved fully upon radical resection of the tumor. Much of the literature suggests that oncogenic osteomalacia is usually caused by a benign mesenchymal tumor secreting fibroblast growth factor subtype-23 (FGF23) but other phosphatonins are rarely implicated.We have previously reported a seemingly typical case of oncogenic osteomalacia. Following curative neoplasm resection, we now report unique molecular characteristics and biology of this tumor never described before. A 25-year-old man had been diagnosed with severe oncogenic osteomalacia that gradually crippled him over 6 years. 68Ga-DOTA-TATE PET-CT scan localized the culprit tumor to his left sole which on resection revealed a plexiform fibrohistiocytic tumor positive for CD34 and CD163 with osteoclast-like giant cells and scattered stromal dendritic cells within the tumor. Circulating FGF23 which was elevated more than 2-folds declined to undetectable levels 24 hours after surgery. Microarray analysis showed over 150-fold upregulation in FGF23, matrix extracellular phosphoglycoprotein (MEPE) and secreted frizzled-related protein subtype 4 (sFRP4) genes which corresponded to the same proteins overexpressed on Western blots
2020-10-30 | GSE160445 | GEO
Project description:ContextLiterature suggests that oncogenic osteomalacia is usually caused by a benign mesenchymal tumor secreting fibroblast growth factor subtype-23 (FGF-23), but the involvement of other phosphatonins has only been scarcely reported. We have previously published a seemingly typical case of oncogenic osteomalacia. Following curative neoplasm resection, we now report unique molecular characteristics and biology of this tumor.Case descriptionA 25-year-old man had been diagnosed with severe oncogenic osteomalacia that gradually crippled him over 6 years. 68Ga-DOTA-TATE positron emission tomography/computed tomography scan localized the culprit tumor to his left sole, which on resection revealed a deep fibrous histiocytoma displaying a proliferation of spindle cells with storiform pattern associated with multinucleated giant cells resembling osteoclasts. Circulating FGF-23, which was elevated more than 2-fold, declined to undetectable levels 24 h after surgery. Microarray analysis revealed increased tumor gene expression of the phosphatonins FGF-23, matrix extracellular phosphoglycoprotein (MEPE) and secreted frizzled-related protein subtype 4, with elevated levels of all 3 proteins confirmed through immunoblot analysis. Differential expression of genes involved in bone formation and bone mineralization were further identified. The patient made an astonishing recovery from being wheelchair bound to fully self-ambulant 2 months postoperatively.ConclusionThis report describes oncogenic osteomalacia due to a deep fibrous histiocytoma, which coincidentally has been found to induce profound muscle weakness via the overexpression of 3 phosphatonins, which resolved fully upon radical resection of the tumor. Additionally, genes involved in bone formation and bone remodeling contribute to the molecular signature of oncogenic osteomalacia.
| S-EPMC8063243 | biostudies-literature
Project description:In soft tissue sarcomas, diagnosis of malignant fibrous histiocytoma (MFH) has been a very controversial issue, and MFH is now considered to be reclassified into pleomorphic subtypes of other sarcomas. To characterize and reclassify MFH genetically, we analyzed gene expression in 105 samples from ten types of soft tissue tumors. Keywords: myxofibrosarcoma, leiomyosarcoma, malignant peripheral nerve sheath tumor, fibrosarcoma, malignant fibrous histiocytoma
2007-04-01 | GSE6481 | GEO
Project description:Comparative genomic hybridisation of 33 human malignant fibrous histiocytoma tumours using a homemade 1 Mb BAC/PAC genomic microarray
2011-01-01 | E-MEXP-1804 | biostudies-arrayexpress
Project description:In soft tissue sarcomas, diagnosis of malignant fibrous histiocytoma (MFH) has been a very controversial issue, and MFH is now considered to be reclassified into pleomorphic subtypes of other sarcomas. To characterize and reclassify MFH genetically, we analyzed gene expression in 105 samples from ten types of soft tissue tumors. Experiment Overall Design: Gene expression of 105 soft tissue tumor samples consisting of synovial sarcoma (n=16), myxoid liposarcoma (n=19), lipoma (n=3), well-differentiated liposarcoma (n=3), dedifferentiated liposarcoma (n=15), myxofibrosarcoma (n=15), leiomyosarcoma (n=6), malignant peripheral nerve sheath tumor (n=3), fibrosarcoma (n=4) and malignant fibrous histiocytoma (n=21) were analyzed using an Affymetrix HG-U133A array.
2008-11-22 | E-GEOD-6481 | biostudies-arrayexpress
Project description:We are currently studying the mechanisms that confer tumour initiating potential upon SP, and as part of this work, we undertook gene profiling studies comparing expression between SP and non-SP cells, initially focusing on the most common soft tissue sarcoma, malignant fibrous histiocytoma (or MFH) Sarcomas contain a subpopulation of cells which exclude Hoechst dye (SP cells) and are enriched for tumor initiating potential. The persistence of SP cells could be responsible for relapse or a failed response to therapy. Expression profiles were compared between the SP and non-SP cells from malignant fibrous histiocytoma (MFH) tumors using microarray. The Hedgehog and Notch pathways were activated in SP cells. Blocking these pathways in MFH xenografts established in NOD-SCID mice depleted the abundance of SP cells and reduced tumor growth. Intriguingly, treatment also substantially inhibited the potential for successful secondary transplantation. The data provides support that SP cells act as tumor initiating cells in sarcomas and suggests targeting the SP as an enticing approach for sarcoma therapy.
2012-01-17 | GSE32375 | GEO
Project description:We are currently studying the mechanisms that confer tumour initiating potential upon SP, and as part of this work, we undertook gene profiling studies comparing expression between SP and non-SP cells, initially focusing on the most common soft tissue sarcoma, malignant fibrous histiocytoma (or MFH) Sarcomas contain a subpopulation of cells which exclude Hoechst dye (SP cells) and are enriched for tumor initiating potential. The persistence of SP cells could be responsible for relapse or a failed response to therapy. Expression profiles were compared between the SP and non-SP cells from malignant fibrous histiocytoma (MFH) tumors using microarray. The Hedgehog and Notch pathways were activated in SP cells. Blocking these pathways in MFH xenografts established in NOD-SCID mice depleted the abundance of SP cells and reduced tumor growth. Intriguingly, treatment also substantially inhibited the potential for successful secondary transplantation. The data provides support that SP cells act as tumor initiating cells in sarcomas and suggests targeting the SP as an enticing approach for sarcoma therapy. In this study, we studied six MFH tumours, and identified a number of signaling pathways that were consistently activated in the SP population compared to the non-SP population.
2012-01-17 | E-GEOD-32375 | biostudies-arrayexpress
Project description:Analysis of undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma like tumors from BrafCa, p53Fl/Fl mouse model of soft tissue sarcoma
2014-12-01 | GSE20049 | GEO
Project description:Analysis of undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma-like tumors from LSL-KrasG12D, p53Fl/Fl mouse model of soft tissue sarcoma.
2009-11-21 | GSE16779 | GEO
Project description:Purpose: Paraneoplastic syndromes occur in cancer patients and originate from dysfunction of organs at a distance from the tumor or its metastasis. In this study, using a Drosophila gut tumor model, we characterized a mechanism of tumor-induced kidney dysfunction. Methods: snRNA-seq analysis of MT samples with and without Yki gut tumors and snRNA-seq analysis of MT samples with kidney principal cell-specific disregulation of PDGF/VEGF signaling Results: we found that Pvf1, a PDGF/VEGF signaling ligand, secreted by gut tumors activates the PvR/JNK/Jra signaling pathway in the principal cells of the kidney, leading to mis-expression of renal genes and paraneoplastic renal syndrome-like phenotypes Conclusions: Our study describes a novel mechanism by which gut tumors perturb the function of the kidney, which might be of clinical relevance for the treatment of paraneoplastic syndromes.
2024-01-18 | GSE251715 | GEO