Similar Datasets
Project description:450K analysis of pediatric histiocytic sarcomas and anteceding hematologic malignancies
| PRJNA432268 | ENA
Project description:Molecular Genetics of Histiocytic Sarcomas
| PRJNA507682 | ENA
Project description:Molecular Genetics of Histiocytic Sarcomas
| PRJNA507681 | 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.
2013-08-07 | GSE45832 | GEO
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:Purpose of reviewRas pathway mutations are one of the most common type of alterations in pediatric hematologic malignancies and are frequently associated with adverse outcomes. Despite ongoing efforts to use targeted treatments, there remain no Food and Drug Administration (FDA)-approved medications specifically for children with Ras pathway-mutated leukemia. This review will summarize the role of Ras pathway mutations in pediatric leukemia, discuss the current state of Ras pathway inhibitors and highlight the most promising agents currently being evaluated in clinical trials.Recent findingsEfficacy using RAF and MEK inhibitors has been demonstrated across multiple solid and brain tumors, and these are now considered standard-of-care for certain tumor types in adults and children. Clinical trials are now testing these medications for the first time in pediatric hematologic disorders, such as acute lymphoblastic leukemia, juvenile myelomonocytic leukemia, and histiocytic disorders. Novel inhibitors of the Ras pathway, including direct RAS inhibitors, are also being tested in clinical trials across a spectrum of pediatric and adult malignancies.SummaryActivation of the Ras pathway is a common finding in pediatric hematologic neoplasms. Implementation of precision medicine with a goal of improving outcomes for these patients will require testing of Ras pathway inhibitors in combination with other drugs in the context of current and future clinical trials.
| S-EPMC7880552 | biostudies-literature
Project description:Pediatric sarcomas present heterogeneous morphology, genetics and clinical behavior posing a challenge for an accurate diagnosis. DNA methylation is an epigenetic modification that coordinates chromatin structure and regulates gene expression, determining cell type and function. DNA methylation-based tumor profiling classifier for sarcomas (known as sarcoma classifier) from the German Cancer Research Center (Deutsches Krebsforschungszentrum) was applied to 122 pediatric sarcomas referred to a reference pediatric oncology hospital. The classifiers reported 88.5% of agreement between histopathological and molecular classification confirming the initial diagnosis of all osteosarcomas and Ewing sarcomas. Transcriptome raw data quality was verified with FASTQC. We used STAR-fusion to identify and annotate fusion transcripts based on discordant read alignments with default configurations. ChimeraViz was used to plot fusion-genes.
2024-11-05 | GSE275159 | GEO
Project description:A complex interplay of intracellular signaling networks orchestrates normal cell growth and survival, including translation, transcription, proliferation, and cell cycle progression. Dysregulation of such signals occurs commonly in many malignancies, thereby giving the cancer cell a survival advantage, but also providing possible targets for therapeutic intervention. Activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway contributes to the proliferative advantage of malignant cells and may confer resistance to chemotherapy in various hematologic malignancies. The initial mTOR inhibitor, sirolimus (also known as rapamycin), was first discovered in 1975 in the soil of Easter Island. Sirolimus was originally developed as an anti-fungal agent given its macrolide properties, but was approved by the Food and Drug Administration (FDA) in 1999 as an immunosuppressive agent for renal transplantation patients once its T cell suppression characteristics were recognized. Shortly thereafter, recognition of sirolimus's ability to inhibit cellular proliferation and cell cycle progression brought sirolimus to the forefront as a possible inhibitor of mTOR. In the subsequent decade, the functional roles of the mTOR protein have been more fully elucidated, and this protein is now known to be a key regulator in a highly complex signaling pathway that controls cell growth, proliferation, metabolism, and apoptosis. This article discusses the dysregulation of PI3K/mTOR signaling in hematologic malignancies, including acute and chronic leukemias, lymphomas, and lymphoproliferative disorders. The current repertoire of PI3K/mTOR pathway inhibitors in development and clinical trials to date are described with emphasis upon pediatric hematologic malignancies (Figure 1). Investigation of small molecule inhibitors of this complex signaling network is an active area of oncology drug development.
| S-EPMC4032892 | biostudies-literature
Project description:Compare a single sample run with two different technologies: Illumina 450k methylation array and MIRA on NimbleGen
2013-06-08 | GSE42707 | GEO
Project description:As CAR T-cell therapy has advanced in B-cell acute lymphoblastic leukemia, research is now underway to develop similar therapies for other lymphoid and myeloid malignancies for pediatric patients. Barriers, including antigen selection and on-target/off-tumor toxicity, have prevented the rapid development of immune-based therapies for T-lineage and myeloid malignancies. More recently, unique strategies have been developed to overcome these barriers, with several products advancing to clinical trials. For T-lineage diseases, targets have focused on CD5, CD7, and CD38, whereas myeloid disease targets have predominately focused on CD123, CD33, and, more recently, CLL-1. This review provides a comprehensive overview of these targets and approaches to overcoming safety concerns in the development of CAR T-cell therapies for pediatric patients with T-lineage and myeloid malignancies.
| S-EPMC7727568 | biostudies-literature