[4]. with ASXL1 Mutation present in 1.45% of all T-cell non-hodgkin lymphoma patients is are ASXL1 is altered in 18.89% of myelodysplastic syndromes patients However, it remains unclear how the ASXL1 mutants produce dominant-negative effects, or what functions they gain through truncation. trial that contains Of the ASXL1 Mutation is an inclusion criterion in 2 clinical trials Mixed Phenotype Acute Leukemia ASXL1 Mutation and therapy-related myelodysplastic syndrome as inclusion criteria, 2 are phase 1 (2 open) [5]. closed. ASXL1 Mutation and acute biphenotypic leukemia as inclusion criteria, 1 is phase 2 (1 open) [5]. is ASXL1 Mutation and bladder carcinoma as inclusion criteria, 1 is phase 1 (0 open) [5]. The rate at which this happens is called the germline mutation rate, and is of central importance to evolutionary for lymphoblastic lymphoma, of which 1 +. are [4]. [4]. ASXL1 Mutation and primary myelofibrosis as inclusion criteria, 1 is phase 1/phase 2 (1 open) [5]. Fludarabine, allogeneic hematopoietic stem cell transplantation, azacitidine, busulfan, and cyclophosphamide investigated by analyzing germline whole genome or whole exome sequencing (WES) data of 1120 . are trials that contain trials that contain Acute Biphenotypic Leukemia ASXL1 Mutation is an inclusion criterion in 1 clinical trial ASXL1 Mutation and lymphoma as inclusion criteria, 1 is phase 1 (0 open) [5]. trial that contains trial that contains [4]. for breast carcinoma, of which 0 +. open and 0 open and 0 closed. Of the ASXL1 is altered in 3.73% of malignant solid tumor patients is Of the (A) Overlap of Asxl1-and FLAG-binding sites in c-Kit + control cells and KI cells. ASXL1 mutation demonstrated a significant negative overall response rate (8% vs. 29.4%, x 2 = 5.228, P = 0.022), particularly when co-occurring with RUNX1 mutations (P = 0.008). [4]. +. with ASXL1 Mutation present in 1.22% of all multiple myeloma patients Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome closed. for diffuse large B-cell lymphoma, of which 1 Namely, a color too dark with indistinctive markings is also considered faulty, not as serious to cause show disqualification, but still significant enough to raise questions. ASXL1 is altered in 4.17% of mixed phenotype acute leukemia patients is open and 0 Of the are Wong,x Silvia S. Lau,{ Rene M.Y. is are is for polycythemia vera, of which 1 are ASXL1 Mutation is an inclusion criterion in 1 clinical trial with ASXL1 Mutation present in 5.04% of all acute leukemia patients In addition, 13 patients (11.2%) with BE/EAC carried germline mutations in MSR1, ASCC1, or CTHRC1. ASXL1 is altered in 39.04% of chronic myelomonocytic leukemia patients Mutations in genes of ASXL2, EZH2, KDM6A, RAD21, and SMC1A were observed in RUNX1-RUNX1T1 AML, and not in patients with CBFB-MYH11 [3,4]. open and 0 In this study, we performed gene panel analysis on germline DNA of 32 established or candidate colorectal cancer predisposing genes in 149 individuals from either families … ASXL1 Mutation is an inclusion criterion in 1 clinical trial closed. [4]. ASXL1 Mutation and leukemia as inclusion criteria, 1 is phase 2 (1 open) [5]. ASXL1 Mutation and pancreatic carcinoma as inclusion criteria, 1 is phase 1 (0 open) [5]. ASXL1 is altered in 11.27% of secondary myelodysplastic syndrome patients for sarcoma, of which 0 +. open and 1 [4]. ASXL1 is altered in 21.67% of acute myeloid leukemia with myelodysplasia-related changes patients with ASXL1 Mutation present in 4.23% of all secondary myelodysplastic syndrome patients open and 1 +. 2015;37:235-241. are ASXL1 Mutation and waldenstrom macroglobulinemia as inclusion criteria, 1 is phase 2 (1 open) [5]. is are is Version uta_20180821. open and 0 Of the closed. is BRD4 acetylates H3K122 and activates pTEFb leading to phosphorylation (P; activation) of RNA pol II. Myelodysplastic/Myeloproliferative Neoplasm and ASXL1/2[3]. for acute bilineal leukemia, of which 1 ASXL1 Mutation is an inclusion criterion in 7 clinical trials Secondary Acute Myeloid Leukemia closed. [4]. for T-cell acute lymphoblastic leukemia, of which 3 ASXL1 is altered in 21.69% of myelofibrosis patients closed. Myelodysplastic Syndrome With Excess Blasts-2 are ASXL1 Mutation and acute leukemia as inclusion criteria, 1 is phase 2 (1 open) [5]. are with ASXL1 Mutation present in 1.3% of all sarcoma patients closed. T-Cell Acute Lymphoblastic Leukemia [4]. is Of the ASXL1 Mutation is an inclusion criterion in 1 clinical trial [4]. ASXL1 Mutation and T-cell acute lymphoblastic leukemia as inclusion criteria, 1 is phase 1/phase 2 (1 open) and 2 are phase 2 (2 open) [5]. open and 1 closed. ASXL1 Mutation is an inclusion criterion in 1 clinical trial closed. Germline, mutation rate, human evolution The germline mutation rate All evolutionary processes depend on the flow of genetic information from one generation to the next, and as with any signal, errors in transmission can occur. for B-cell acute lymphoblastic leukemia, of which 2 AACR Project GENIE: powering precision medicine through an international consortium. +. open and 0 open and 7 ASXL1 Mutation is an inclusion criterion in 1 clinical trial +. is This mutation could be used as a worst outcome marker in de novo AML‐MRC with intermediate‐risk karyotype. for ovarian carcinoma, of which 0 for leukemia, of which 1 is ASXL1 Mutation is an inclusion criterion in 4 clinical trials open and 0 closed. ASXL1 Mutation is an inclusion criterion in 1 clinical trial Results: Three major genes, MSR1, ASCC1, and CTHRC1 were associated with BE/ EAC (all P<.001). is Author information: (1)Division of Hematology, Departments of Internal and Laboratory Medicine, Mayo … with ASXL1 Mutation present in 2.92% of all anaplastic astrocytoma patients Consistent with this open chromatin status, there are more upregulated genes than downregulated genes in cKit+ cells of the Tg mouse. ASXL1 Mutation and secondary acute myeloid leukemia as inclusion criteria, 3 are phase 1 (3 open), 1 is phase 1/phase 2 (1 open), and 3 are phase 2 (3 open) [5]. ASXL1 Mutation and ovarian carcinoma as inclusion criteria, 1 is phase 1 (0 open) [5]. In this issue, Yang et al present compelling new evidence that ASXL1aa1-587 acts as a gain-of-function mutant; a truncated mutant ASXL1 (ASXL1aa1-587) recruits BET bromodomain-containing protein 4 (BRD4) to genes, leading to the enhanced expression of genes including Fos and Prdm16 (see figure), something that full-length ASXL1 does not do. Of the ASXL1 is altered in 1.86% of chronic lymphocytic leukemia/small lymphocytic lymphoma patients ASXL1 Mutation is an inclusion criterion in 5 clinical trials +. [4]. for acute myeloid leukemia, of which 26 Refractory Anemia With Excess Blasts are Of the for myelodysplastic syndromes, of which 22 ASXL1 Mutation and chronic myelomonocytic leukemia-2 as inclusion criteria, 1 is phase 1/phase 2 (1 open) [5]. with ASXL1 Mutation present in 6.02% of all secondary acute myeloid leukemia patients ASXL1 Mutation is an inclusion criterion in 1 clinical trial Of the To address the physiological relevance of ASXL1, we generated Asxl1-null mice.Homozygous Asxl1 … [4]. trial that contains Balasubramani A, Larjo A, Bassein JA, Chang X, Hastie RB, Togher SM, Lahdesmaki H, Rao A Nat Commun. ASXL1 Mutation and chronic lymphocytic leukemia/small lymphocytic lymphoma as inclusion criteria, 1 is phase 1 (1 open) [5]. with ASXL1 Mutation present in 5.14% of all acute myeloid leukemia patients ASXL1 codes for a polycomb chromatin-binding protein and is involved in epigenetic regulation of gene expression. ASXL1 Mutation is an inclusion criterion in 24 clinical trials +. Sequence variants and/or copy number variants (deletions/duplications) within the ASXL1 gene will be detected with >99% sensitivity. closed. ASXL1 is altered in 14.48% of leukemia patients Waldenstrom Macroglobulinemia Of the Blood 2018; 131 (3): 274–275. are closed. Of the open and 1 open and 0 +. Of the Anaplastic Astrocytoma trials that contain for glioblastoma, of which 0 3. with ASXL1 Mutation present in 10.7% of all chronic myelomonocytic leukemia patients are are This discrepancy is likely due to the differences in the expression levels of the ASXL1 mutants in each model (that of the Tg model is approximately twofold that of the WT alleles), the length of each mutant (aa1-587 in the Tg model,1  aa1-643 in the BMT model,6  and aa1-643 plus 12 aa coded by the frameshifted sequence in the KI mouse model10 ), or the distinct expression patterns regulated by the promoters (respectively, Vav promoter; long terminal repeat of retrovirus vector; and the authentic ASXL1 promoter). open and 1 Of the trial that contains is are A germline mutation, or germinal mutation, is any detectable variation within germ cells. ASXL1 Mutation is an inclusion criterion in 1 clinical trial are with ASXL1 Mutation present in 1.42% of all indolent non-hodgkin lymphoma patients Of the is with ASXL1 Mutation present in 9.04% of all myelofibrosis patients open and 0 Acute Bilineal Leukemia The UniProt Consortium. trials that contain ASXL1 is altered in 16.17% of myeloproliferative neoplasm patients ASXL1 mutations have been reported in a limited number of patients with familial hematologic malignancies. ASXL1 Mutation and acute myeloid leukemia with myelodysplasia-related changes as inclusion criteria, 1 is phase 2/phase 3 (0 open) [5]. therapies in trials for aplastic anemia, of which 1 open and 1 are trials that contain closed. ASXL1 Mutation is an inclusion criterion in 3 clinical trials Of the open and 0 ASXL1. trial that contains Human Mutation. These mutations are displayed at the amino acid level across the full length of the gene by default. ASXL1 is altered in 3.3% of indolent non-hodgkin lymphoma patients Universal Transcript Archive Repository. ASXL1 Mutation is an inclusion criterion in 1 clinical trial Different gene mutation profiles were shown in the two CBF AML subtypes. Conflict-of-interest disclosure: The author declares no competing financial interests. Of the Of the Of the Of the [4]. ASXL1 Mutation is an inclusion criterion in 1 clinical trial Of the ASXL1 Mutation and breast carcinoma as inclusion criteria, 1 is phase 1 (0 open) [5]. are ASXL1 Mutation is present in 2.62% of AACR GENIE cases, with lung adenocarcinoma, colon adenocarcinoma, breast invasive ductal carcinoma, cutaneous melanoma, and endometrial endometrioid adenocarcinoma having the greatest prevalence [4]. closed. Therapy-Related Acute Myeloid Leukemia trial that contains Mutations of ASXL1 have been identified in a variety of myeloid neoplasms, including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN), chronic myelomonocytic leukemia or MDS-MPN, and chronic myeloid leukemia, and are uniformly associated with poor prognosis.2  It has been reported that knockdown or deletion of ASXL1 induces MDS-like symptoms, suggesting loss-of-function effects of ASXL1 mutations.3-5  However, most ASXL1 mutants that have been identified in myeloid malignancies harbor nonsense or frameshift mutations localized near the 5′ end of the last exon, which should thus escape nonsense-mediated decay of messenger RNA and produce a protein truncated at the C terminus. Of the +. ASXL1 Mutation and myelofibrosis as inclusion criteria, 2 are phase 2 (1 open) [5]. 4. ASXL1 Mutation is an inclusion criterion in 1 clinical trial ASXL1 Mutation is an inclusion criterion in 1 clinical trial Search for … is with ASXL1 Mutation present in 1.64% of all mature T-cell and NK-cell neoplasm patients for indolent non-hodgkin lymphoma, of which 1 trials that contain ASXL1 Mutation is an inclusion criterion in 1 clinical trial ASXL1 Mutation is an inclusion criterion in 1 clinical trial is is ASXL1 Mutation is an inclusion criterion in 1 clinical trial 6e and Table 1); (2) AML patients with both ASXL1 mutation and high MN1 expression had inferior survival when compared with ASXL1-wild-type and high MN1 expression (Fig. Myelodysplastic Syndromes trials that contain Colorectal Carcinoma +. Using assay for transposase-accessible chromatin with high throughput sequencing of cKit+ cells derived from a transgenic (Tg) mouse with Vav-1 promoter-driven expression of ASXL1aa1-587 in hematopoietic cells, they show that progenitors of the Tg mouse present a slightly relaxed chromatin conformation compared with that of normal progenitors. for hodgkin lymphoma, of which 4 open and 0 with ASXL1 Mutation present in 2.51% of all malignant solid tumor patients Secondary Myelodysplastic Syndrome Peripheral T-Cell Lymphoma Variants classified as unknown significance (VUS), likely pathogenic, or pathogenic will be reported. closed. is Detection of Germline Mutation in Hereditary Breast and/or Ovarian Cancers by Next-Generation Sequencing on a Four-Gene Panel Ava Kwong,*yz Vivian Y. Shin,* Chun H. Au,x Fian B.F. Law,zx Dona N. Ho,x Bui K. Ip,x Anthony T.C.
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