Molecular Genetics of Secondary Histiocytic/Dendritic Sarcoma
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PROVIDER: PRJNA593082 | ENA |
REPOSITORIES: ENA
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Project description:Molecular Genetics of Secondary Histiocytic/Dendritic Sarcoma
| PRJNA593083 | ENA
Project description:Molecular Genetics of Histiocytic Sarcomas
| PRJNA507681 | ENA
Project description:Molecular Genetics of Histiocytic Sarcomas
| PRJNA507682 | ENA
Project description:Background: The determination of altered expression of genes in specific tumor types and their effect upon cellular processes may create insight in tumorigenesis and help to design better treatments. The Flatcoated retriever is a dog breed with an exceptionally high incidence of histiocytic sarcomas. The breed develops two distinct entities of histiocytic neoplasia, a soft tissue form and a visceral form. Gene expression studies of these tumors has value for comparable human diseases such as histiocytic/dendritic cell sarcoma for which knowledge is difficult to accrue due to their rare occurrence. In addition, such studies may help in the search for genetic aberrations underlying the genetic predisposition in this dog breed. Methods: Microarray analysis and pathway analyses were performed on fresh-frozen tissues obtained from Flatcoated retrievers with localized, soft tissue histiocytic sarcomas (STHS) and disseminated, visceral histiocytic sarcomas (VHS) and on normal canine spleens from various breeds. Expression differences of nine genes were validated with quantitative real-time PCR (qPCR) analyses. Results: QPCR analyses identified the significantly altered expression of nine genes; PPBP, SpiC, VCAM1, ENPEP, ITGAD (down-regulated), and GTSF1, Col3a1, CD90 and LUM (up-regulated) in the comparison of both the soft tissue and the visceral form with healthy spleen. DAVID pathway analyses revealed 24 pathways that were significantly involved in the development of HS in general, most of which were involved in the DNA repair and replication process. Conclusions: This study identified altered expression of nine genes not yet implicated in histiocytic sarcoma manifestations in the dog nor in comparable human histiocytic/dendritic sarcomas. Extraploration of this downside effect of canine inbreeding strategies for the study of similar sarcomas in humans might also lead to the identification of genes related to these rare malignancies in the human. Microarray expression dataset including STHS: Soft Tissue (localized) Histiocytic Sarcoma; VHS: Visceral (disseminated)Histiocytic Sarcoma; together with normal spleen (NS) samples. Comparisons were analysed in dyeswap on a 2-color platform against a common reference sample, consisting of a multitude of canine organs, including liver, spleen, kidney, lung, hart, intestine and bone.
2013-08-07 | E-GEOD-45832 | biostudies-arrayexpress
Project description:Background: The determination of altered expression of genes in specific tumor types and their effect upon cellular processes may create insight in tumorigenesis and help to design better treatments. The Flatcoated retriever is a dog breed with an exceptionally high incidence of histiocytic sarcomas. The breed develops two distinct entities of histiocytic neoplasia, a soft tissue form and a visceral form. Gene expression studies of these tumors has value for comparable human diseases such as histiocytic/dendritic cell sarcoma for which knowledge is difficult to accrue due to their rare occurrence. In addition, such studies may help in the search for genetic aberrations underlying the genetic predisposition in this dog breed. Methods: Microarray analysis and pathway analyses were performed on fresh-frozen tissues obtained from Flatcoated retrievers with localized, soft tissue histiocytic sarcomas (STHS) and disseminated, visceral histiocytic sarcomas (VHS) and on normal canine spleens from various breeds. Expression differences of nine genes were validated with quantitative real-time PCR (qPCR) analyses. Results: QPCR analyses identified the significantly altered expression of nine genes; PPBP, SpiC, VCAM1, ENPEP, ITGAD (down-regulated), and GTSF1, Col3a1, CD90 and LUM (up-regulated) in the comparison of both the soft tissue and the visceral form with healthy spleen. DAVID pathway analyses revealed 24 pathways that were significantly involved in the development of HS in general, most of which were involved in the DNA repair and replication process. Conclusions: This study identified altered expression of nine genes not yet implicated in histiocytic sarcoma manifestations in the dog nor in comparable human histiocytic/dendritic sarcomas. Extraploration of this downside effect of canine inbreeding strategies for the study of similar sarcomas in humans might also lead to the identification of genes related to these rare malignancies in the human.
2013-08-07 | GSE45832 | GEO
Project description:The differential diagnosis between histiocytic sarcoma (HS) and undifferentiated pleomorphic sarcoma (UPS) remains an underexplored area of histopathological and oncological relevance. Both entities are rare, high-grade neoplasms that may arise in soft tissue, skin, the nervous system, and the gastrointestinal tract, among other sites, predominantly in adult patients. Their clinical and morphological overlap may be underrecognized, partly due to the subspecialized structure of contemporary surgical pathology practice. Comparative data on their natural history, treatment, and prognosis remain limited. Furthermore, while UPS is managed according to established international guidelines, no standardized treatment approach exists for HS. In this study, we compared the clinical, histopathological, and genetic features of three patient groups diagnosed with HS, UPS, and dedifferentiated liposarcoma (DLS) – control group. In a “real-life” diagnostic setting, we explore their diagnostic relevance, applying a comprehensive, multi-platform approach, including immunophenotyping, high-throughput sequencing, gene expression profiling, and methylome analysis. We demonstrated a substantial morphophenotypic overlap among the three neoplasms, while also identifying distinct features within each group. Histiocytic sarcoma samples were enriched for mutations in the MAPK pathway, along with other recurrent mutations characteristic of myeloid neoplasms, and exhibited a functional genetic signature consistent with derivation from mononuclear phagocytes. In contrast, soft tissue sarcomas showed a markedly higher tumor mutational burden and evidence of Hippo pathway activation, as well as FGF/FGFR signaling. Our work represents an initial step toward establishing a comprehensive diagnostic framework for malignant histiocytosis, facilitating the identification of relevant therapeutic and prognostic factors, and ultimately improving the clinical management of these rare patients.
2026-06-23 | GSE335879 | GEO
Project description:The objective of this study was to compare the transcriptomes of uninfected DH82 cells, a canine histiocytic sarcoma cell line, with DH82 cells, persistently infected with the Onderstepoort strain of canine distemper virus in order to identify effects of canine distemper virus infection upon the transcriptome of this tumor cell line and hereby draw conclusions on possible paramyxovirus-induced oncolytic mechanisms
2016-12-02 | E-MTAB-3942 | biostudies-arrayexpress
Project description:Multi-omics profiling supports the diagnosis of histiocytic sarcoma and mesenchymal mimics
| PRJNA1479746 | ENA
Project description:Histiocytic neoplasms are clonal, hematopoietic disorders characterized by an accumulation of abnormal, monocyte-derived dendritic cells or macrophages in Langerhans Cell (LCH) and non-Langerhans (non-LCH) histiocytoses, respectively. The discovery of BRAFV600E mutations in ~50% of these patients provided the first molecular therapeutic target in histiocytosis. However, recurrent driving mutations in the majority of BRAFV600E-wildtype, non-LCH patients are unknown, and recurrent cooperating mutations in non-MAP kinase pathways are undefined for the histiocytic neoplasms. Through combined whole exome and transcriptome sequencing, we identified recurrent kinase fusions involving BRAF, ALK, and NTRK1, as well as recurrent, activating MAP2K1 and ARAF mutations in BRAFV600E-wildtype, non-LCH patients. In addition to MAP kinase pathway lesions, recurrently altered genes involving diverse cellular pathways were identified. Treatment of MAP2K1- and ARAF-mutated, non-LCH patients using MEK and RAF inhibitors, respectively, resulted in clinical efficacy demonstrating the importance of detecting and targeting diverse kinase alterations in these disorders. 13 patient samples were analyzed by RNA-seq and had 2 replicates.
2015-11-11 | E-GEOD-74442 | biostudies-arrayexpress
Project description:Histiocytic neoplasms are clonal, hematopoietic disorders characterized by an accumulation of abnormal, monocyte-derived dendritic cells or macrophages in Langerhans Cell (LCH) and non-Langerhans (non-LCH) histiocytoses, respectively. The discovery of BRAFV600E mutations in ~50% of these patients provided the first molecular therapeutic target in histiocytosis. However, recurrent driving mutations in the majority of BRAFV600E-wildtype, non-LCH patients are unknown, and recurrent cooperating mutations in non-MAP kinase pathways are undefined for the histiocytic neoplasms. Through combined whole exome and transcriptome sequencing, we identified recurrent kinase fusions involving BRAF, ALK, and NTRK1, as well as recurrent, activating MAP2K1 and ARAF mutations in BRAFV600E-wildtype, non-LCH patients. In addition to MAP kinase pathway lesions, recurrently altered genes involving diverse cellular pathways were identified. Treatment of MAP2K1- and ARAF-mutated, non-LCH patients using MEK and RAF inhibitors, respectively, resulted in clinical efficacy demonstrating the importance of detecting and targeting diverse kinase alterations in these disorders.
2015-11-11 | GSE74442 | GEO