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99 results for “WT1”
Data from: Long-term severe hypoxia adaptation induces non-canonical EMT and a novel Wilms Tumor 1 (WT1) isoform
<p>The majority of cancer deaths are caused by solid tumors, where the four most prevalent cancers (breast, lung, colorectal and prostate) account for more than 60% of all cases (1). Tumor cell heterogeneity driven by variable cancer microenvironments, such as hypoxia, is a key determinant of therapeutic outcome. We developed a novel culture protocol, termed the Long-Term Hypoxia (LTHY) time course, to recapitulate the gradual development of severe hypoxia seen in vivo to mimic conditions observed in primary tumors. Cells subjected to LTHY underwent a non-canonical epithelial to mesenchymal transition (EMT) based on miRNA and mRNA signatures as well as displayed EMT-like morphological changes. Concomitant to this, we report production of a novel truncated isoform of WT1 transcription factor (tWt1), a non-canonical EMT driver, with expression driven by a yet undescribed intronic promoter through hypoxia-responsive elements (HREs). We further demonstrated that tWt1 initiates translation from an intron-derived start codon, retains proper subcellular localization and DNA binding. A similar tWt1 is also expressed in LTHY-cultured human cancer cell lines as well as primary cancers and predicts long-term patient survival. Our study not only demonstrates the importance of culture conditions that better mimic those observed in primary cancers, especially with regards to hypoxia, but also identifies a novel isoform of WT1 which correlates with poor long-term survival in ovarian cancer.</p>
Framework of clonal mutations concurrent with WT1 mutations in adults with acute myeloid leukemia (Alliance)
<p>Mutations affecting the tumor suppressor gene, WT1 transcription factor (<em>WT1</em>) are relatively common in adults with acute myeloid leukemia (AML) and have been reported to associate with a poor prognosis. However, there is limited data describing additional mutations co-occurring with <em>WT1</em> as well as clonal architecture and complexity. We performed targeted DNA sequencing on 96 pretreatment samples from adult patients with <em>de novo</em> AML who harbored <em>WT1</em> mutations and subsequently performed single-cell DNA sequencing on a subset of these samples. <em>FLT3</em>-ITD mutations were the most common co-occurring mutations detected in 47% of <em>WT1</em>-mutated patients (<em>WT1<sup>mut</sup></em>/<em>FLT3</em>-ITD). Among <em>WT1<sup>mut</sup></em>/<em>FLT3</em>-ITD patients, <em>NPM1</em> mutations were observed in 58% of patients. In contrast, patients with <em>WT1</em>-mutated AML but no <em>FLT3</em>-ITD (<em>WT1<sup>mut</sup></em>/no <em>FLT3</em>-ITD) had significantly more frequent mutations in alternative signal activating pathways (<em>FLT3</em>-TKD: 25% vs 11%; and NRAS: 37% vs 11%) compared with <em>WT1<sup>mut</sup></em>/<em>FLT3</em>-ITD patients, and, notably, fewer mutations in <em>NPM1</em> (16% vs 58%). Given the difference in NRAS mutation frequency in <em>WT1<sup>mut</sup></em>/<em>FLT3</em>-ITD compared to <em>WT1<sup>mut</sup></em>/no <em>FLT3</em>-ITD patients, we then compared the variant allele frequencies (VAF) of <em>NRAS</em> mutations in the presence or absence of FLT3 mutations. There was a trend for higher NRAS VAF in <em>WT1</em>-mutated patients with concurrent <em>NRAS</em> mutations but no <em>FLT3</em> mutations (<em>FLT3</em>-WT), suggesting this may be due to WT1 being the founding mutation with two or more distinct sub-clones. To further delineate this observation, we performed single-cell DNA sequencing on seven samples with co-occurring <em>WT1</em> and <em>NRAS</em> mutations with or without <em>FLT3</em> mutations. Single-cell sequencing revealed that <em>WT1</em> mutations were more frequently observed in the founder clone (6 out of 7 samples), with or without <em>NPM1</em> mutations. Five of the seven samples included in the single-cell sequencing harbored both a <em>FLT3</em> (ITD or TKD) and an <em>NRAS</em> mutation. The analysis shows these mutations arose in mutually exclusive sub-clones from a <em>WT1</em> mutated founder clone in all 5 cases. These data, to our knowledge, represent the largest series of adults with <em>WT1</em>-mutated AML, and for the first time describe clonal architecture and the combination of mutations co-occurring in single cells. These data provide a deeper understanding of the genomic complexity and biology of <em>WT1</em>-mutated AML and may provide insight into the future development of novel therapeutic strategies.</p>
CT7, MAGE-A3, and WT1 mRNA-electroporated Autologous Langerhans-type Dendritic Cells as Consolidation for Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation
ClinicalTrials.gov study NCT01995708. IPD Sharing: Not stated. Countries: 1. Publications: 1.
Evaluation of an Anti-cancer Immunotherapy Combined With Standard Neoadjuvant Treatment in Patients With WT1-positive Primary Invasive Breast Cancer
ClinicalTrials.gov study NCT01220128. IPD Sharing: YES. Countries: 7. Publications: 1.
WT1 Vaccine Treatment of Patients in Remission From Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL)
ClinicalTrials.gov study NCT01266083. IPD Sharing: NO. Countries: 1. Publications: 1.
WT1 Vaccine Treatment of Patients With Multiple Myeloma After Autologous Stem Cell Transplantation
ClinicalTrials.gov study NCT01827137. IPD Sharing: NO. Countries: 1. Publications: 0.
Wilm's Tumor 1 (WT1) Peptide Vaccine for High Risk Hematologic Malignancy
ClinicalTrials.gov study NCT00433745. IPD Sharing: Not stated. Countries: 1. Publications: 2.
Data from: Long-term severe hypoxia adaptation induces non-canonical EMT and a novel Wilms Tumor 1 (WT1) isoform
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Framework of clonal mutations concurrent with WT1 mutations in adults with acute myeloid leukemia (Alliance)
Open the record for dataset details and reuse information.
WT1 targeting multi-epitope vaccine design for glioblastoma multiforme using immuno-informatics approaches
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A WT1-positive pleural neoplasm. Is it always a mesothelioma? Diagnostic pitfall of WT1 immunohistochemistry in pleural neoplasm
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Registry for Patients With Wilms' Tumor Suppressor Gene 1 (WT1) Mutation Associated Diseases
ClinicalTrials.gov study NCT01252901. IPD Sharing: Not stated. Countries: 1. Publications: 8.
WT1 Peptide Vaccination in Acute Myeloid Leukemia (AML)
ClinicalTrials.gov study NCT00153582. IPD Sharing: Not stated. Countries: 1. Publications: 1.
Safety and Immunogenicity of Recombinant WT1 Antigen-Specific Cancer Immunotherapeutic Combined With Infusion of Treg Depleted T Cells for Adult WT1 Acute Myeloid Leukemia
ClinicalTrials.gov study NCT01513109. IPD Sharing: Not stated. Countries: 1. Publications: 34.
WT1 Immunity Via DNA Fusion Gene Vaccination in Haematological Malignancies by Intramuscular Injection Followed by Intramuscular Electroporation
ClinicalTrials.gov study NCT01334060. IPD Sharing: Not stated. Countries: 1. Publications: 2.
WT1 Peptid Vaccination in Carcinomas
ClinicalTrials.gov study NCT00153608. IPD Sharing: Not stated. Countries: 1. Publications: 1.
Study of ASP7517 Alone and With Pembrolizumab in Participants With Advanced Solid Tumors Expressing WT1 Antigen
ClinicalTrials.gov study NCT04837196. IPD Sharing: NO. Countries: 1. Publications: 0.
Classification of a frameshift/extended and a stop mutation in WT1 as gain of function mutations which activate cell cycle genes and promote Wilms tumor cell proliferation
GEO Series GSE54635. Homo sapiens. 6 samples. Type: Expression profiling by array.
Transcriptomic analysis of embryonic hearts with conditional deletion of Wt1
GEO Series GSE178220. Mus musculus. 6 samples. Type: Expression profiling by high throughput sequencing.
Wilms Tumor cells with WT1 mutations have characteristic features of mesenchymal stem cells
GEO Series GSE18058. Homo sapiens. 29 samples. Type: Expression profiling by array.
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Allen Brain Atlas
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DANDI Archive for NWB datasets
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The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
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