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https://www.readbyqxmd.com/read/28731140/integrated-analysis-of-genome%C3%A2-wide-gene-expression-and-dna-methylation-microarray-of-diffuse-large-b%C3%A2-cell-lymphoma-with-tet-mutations
#1
Pengfei Liu, Wenhua Jiang, Jinkun Zhao, Huilai Zhang
Diffuse large B-cell lymphoma (DLBCL), the most frequently occurring type of lymphoid malignancy, has been demonstrated to be associated with mutations of Ten‑Eleven Translocation (TET). In order to explore the association between DLBCL and TET mutations, the present study analyzed the gene expression and methylation profiles in human DLBCL biopsy tissues with wildtype and mutated TET2. The microarray dataset GSE37365, containing two subseries: the genome‑wide gene expression dataset GSE37362 and the DNA methylation microarray dataset GSE37363, was downloaded from the Gene Expression Omnibus database...
July 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28718760/cd25-expression-and-outcomes-in-older-patients-with-acute-myelogenous-leukemia-treated-with-plerixafor-and-decitabine
#2
John N Allan, Gail J Roboz, Gulce Askin, Ellen Ritchie, Joseph Scandura, Paul Christos, Duane C Hassane, Monica L Guzman
We investigated CD25 expression in older (≥60 years) patients with new acute myelogenous leukemia treated with decitabine and plerixafor. Patients resistant to therapy or survival ≤1 year had significantly higher percentages of CD25(pos) myeloid blasts in baseline bone marrow. CD25(pos) patients had an increased odds of resistance compared to CD25(neg) patients (p = .015). In univariate analysis, we found CD25(pos) patients had inferior survival compared to CD25(neg) (p = .002). In patients with intermediate risk cytogenetics, CD25(pos) status stratified patients associating with inferior survival (p = ...
July 18, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28710961/epigenetic-modification-differences-between-fetal-fibroblast-cells-and-mesenchymal-stem-cells-of-the-arbas-cashmere-goat
#3
Xiao Wang, Zhimin Wang, Qing Wang, Hefei Wang, Hao Liang, Dongjun Liu
To explore the epigenetic mechanisms regulating mesenchymal stem cells, we analyzed epigenetic patterns in control goat fetal fibroblast cells (gFFCs), adipose-derived stem cells (gADSCs), bone marrow stromal cells (gBMSCs), and muscle-derived satellite cells (gMDSCs). We found that the 5mC content of gBMSC genomes was lower than that of gFFC genomes, while the 5mC content of gADSC and gMDSC genomes surpassed that of gFFC genomes. H3K9 acetylation did not differ significantly among those cells; gFFCs, gADSCs, and gMDSCs contained acetylated H3K9, H3K14, H3K18, H4K5, and H4K12, but gBMSCs contained almost no acetylated H4K5 and H4K12...
July 9, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28697999/the-protective-role-of-tet2-in-erythroid-iron-homeostasis-against-oxidative-stress-and-erythropoiesis
#4
Shanqi Guo, Xingkang Jiang, Yuanyuan Wang, Liwei Chen, Huzi Li, Xiaojiang Li, Yingjie Jia
Although previous studies suggested that stress erythropoiesis and iron metabolism regulate each other to increase iron availability for hemoglobin synthesis, the molecular bases determining its different traits remain elusive. In addition, global DNA demethylation has been reported during mouse erythropoiesis in vivo. However, the understanding of iron-related genes through DNA demethylation under stress erythropoiesis is largely unknown. In the current study, we found disordered iron homeostasis and misregulated hepcidin-ferroportin axis under stress erythropoiesis...
July 8, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28691928/mutations-in-5-methylcytosine-oxidase-tet2-and-rhoa-cooperatively-disrupt-t-cell-homeostasis
#5
Shengbing Zang, Jia Li, Haiyan Yang, Hongxiang Zeng, Wei Han, Jixiang Zhang, Minjung Lee, Margie Moczygemba, Sevinj Isgandarova, Yaling Yang, Yubin Zhou, Anjana Rao, M James You, Deqiang Sun, Yun Huang
Angioimmunoblastic T cell lymphoma (AITL) represents a distinct, aggressive form of peripheral T cell lymphoma with a dismal prognosis. Recent exome sequencing in patients with AITL has revealed the frequent coexistence of somatic mutations in the Rho GTPase RhoA (RhoAG17V) and loss-of-function mutations in the 5-methylcytosine oxidase TET2. Here, we have demonstrated that TET2 loss and RhoAG17V expression in mature murine T cells cooperatively cause abnormal CD4+ T cell proliferation and differentiation by perturbing FoxO1 gene expression, phosphorylation, and subcellular localization, an abnormality that is also detected in human primary AITL tumor samples...
July 10, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28677265/epigenetics-in-myeloproliferative-neoplasms
#6
REVIEW
Suzanne McPherson, Mary Frances McMullin, Ken Mills
A decade on from the description of JAK2 V617F, the MPNs are circumscribed by an increasingly intricate landscape. There is now evidence that they are likely the result of combined genetic dysregulation, with several mutated genes involved in the regulation of epigenetic mechanisms. Epigenetic changes are not due to a change in the DNA sequence but are reversible modifications that dictate the way in which genes may be expressed (or silenced). Among the epigenetic mechanisms, DNA methylation is probably the best described...
July 4, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28675510/the-co-regulatory-networks-of-tumor-suppressor-genes-oncogenes-and-mirnas-in-colorectal-cancer
#7
Martha L Slattery, Jennifer S Herrick, Lila E Mullany, Wade S Samowitz, John R Sevens, Lori Sakoda, Roger K Wolff
Tumor suppressor genes (TSGs) and oncogenes (OG) are involved in carcinogenesis. MiRNAs also contribute to cellular pathways leading to cancer. We use data from 217 colorectal cancer (CRC) cases to evaluate differences in TSGs and OGs expression between paired CRC and normal mucosa and evaluate how TSGs and OGs are associated with miRNAs. Gene expression data from RNA-Seq and miRNA expression data from Agilent Human miRNA Microarray V19.0 were used. We focus on genes most strongly associated with CRC (fold change (FC) of ≥1...
July 4, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28669404/ultra-sensitive-sequencing-identifies-high-prevalence-of-clonal-hematopoiesis-associated-mutations-throughout-adult-life
#8
Rocio Acuna-Hidalgo, Hilal Sengul, Marloes Steehouwer, Maartje van de Vorst, Sita H Vermeulen, Lambertus A L M Kiemeney, Joris A Veltman, Christian Gilissen, Alexander Hoischen
Clonal hematopoiesis results from somatic mutations in hematopoietic stem cells, which give an advantage to mutant cells, driving their clonal expansion and potentially leading to leukemia. The acquisition of clonal hematopoiesis-driver mutations (CHDMs) occurs with normal aging and these mutations have been detected in more than 10% of individuals ≥65 years. We aimed to examine the prevalence and characteristics of CHDMs throughout adult life. We developed a targeted re-sequencing assay combining high-throughput with ultra-high sensitivity based on single-molecule molecular inversion probes (smMIPs)...
July 6, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28663574/vitamin-c-induced-epigenomic-remodelling-in-idh1-mutant-acute-myeloid-leukaemia
#9
M Mingay, A Chaturvedi, M Bilenky, Q Cao, L Jackson, T Hui, M Moksa, A Heravi-Moussavi, R K Humphries, M Heuser, M Hirst
The genomes of myeloid malignancies are characterized by epigenomic abnormalities. Heterozygous, inactivating ten-eleven translocation 2 (TET2) mutations and neomorphic isocitrate dehydrogenase (IDH) mutations are recurrent and mutually exclusive in acute myeloid leukaemia genomes. Ascorbic acid (vitamin C) has been shown to stimulate the catalytic activity of TET2 in vitro and thus we sought to explore its effect in a leukaemic model expressing IDH1(R132H). Vitamin C treatment induced an IDH1(R132H)-dependent reduction in cell proliferation and an increase in expression of genes involved in leukocyte differentiation...
June 2, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28660881/ten-eleven-translocation-2-interacts-with-forkhead-box-o3-and-regulates-adult-neurogenesis
#10
Xuekun Li, Bing Yao, Li Chen, Yunhee Kang, Yujing Li, Ying Cheng, Liping Li, Li Lin, Zhiqin Wang, Mengli Wang, Feng Pan, Qing Dai, Wei Zhang, Hao Wu, Qiang Shu, Zhaohui Qin, Chuan He, Mingjiang Xu, Peng Jin
Emerging evidence suggests that active DNA demethylation machinery plays important epigenetic roles in mammalian adult neurogenesis; however, the precise molecular mechanisms and critical functional players of DNA demethylation in this process remain largely unexplored. Ten-eleven translocation (Tet) proteins convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and its downstream derivatives. Here we show that 5hmC is elevated during the differentiation of adult neural stem cells (aNSCs), and Tet2 is primarily responsible for modulating 5hmC dynamics...
June 29, 2017: Nature Communications
https://www.readbyqxmd.com/read/28655780/dnmt3a-and-tet2-dominate-clonal-hematopoiesis-demonstrate-benign-phenotypes-and-different-genetic-predisposition
#11
Manuel Buscarlet, Sylvie Provost, Yassamin Feroz Zada, Amina Barhdadi, Vincent Bourgoin, Guylaine Lépine, Luigina Mollica, Natasha Szuber, Marie-Pierre Dubé, Lambert Busque
Age-associated clonal hematopoiesis caused by acquired mutations in myeloid cancer associated genes is highly prevalent in the normal population. Its etiology, biological impact on hematopoiesis and oncogenic risk is poorly defined at this time. To gain insight into this phenomenon, we analyzed a cohort of 2530 related and unrelated hematologically normal individuals (aged 55 to 101). We used a sensitive gene targeted deep sequencing approach to gain precision on the exact prevalence of driver mutations and the proportions of affected genes...
June 27, 2017: Blood
https://www.readbyqxmd.com/read/28653397/acute-myeloid-leukaemia-genomics
#12
REVIEW
Michael Medinger, Jakob R Passweg
Acute myeloid leukaemia (AML) is a biologically complex, molecularly and clinically heterogeneous disease. Despite major advances in understanding the genetic landscape of AML and its impact on the pathophysiology and biology of the disease, standard treatment options have not significantly changed during the past three decades. AML is characterized by multiple somatically acquired mutations that affect genes of different functional categories. Mutations in genes encoding epigenetic modifiers, such as DNMT3A, ASXL1, TET2, IDH1, and IDH2, are commonly acquired early and are present in the founding clone...
June 27, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28642344/a-role-for-tet2-in-parathyroid-carcinoma
#13
Elham Barazeghi, Anthony J Gill, Stan Sidhu, Olov Norlén, Roberto Dina, F Fausto Palazzo, Per Hellman, Peter Stålberg, Gunnar Westin
Primary hyperparathyroidism (pHPT) is rarely caused by parathyroid carcinoma (PC, <1-5% of pHPT cases). The TET proteins oxidize the epigenetic mark 5-methylcytosine to 5-hydroxymethylcytosine (5hmC) and inactivation by mutation or epigenetic deregulation of TET1 and TET2 play important roles in various cancers. Recently, we found that 5hmC was severely reduced in all of the analyzed PCs and with deranged expression of TET1 for the majority of PCs. Here, we have examined the expression of the TET2 protein in 15 5hmC-negative PCs from patients who had local invasion or metastases...
July 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28642303/molecular-analysis-of-myelodysplastic-syndrome-with-isolated-del-5q-reveals-a-specific-spectrum-of-molecular-mutations-with-prognostic-impact-a-study-on-123-patients-and-27-genes
#14
Manja Meggendorfer, Claudia Haferlach, Wolfgang Kern, Torsten Haferlach
The only cytogenetic aberration defining a myelodysplastic syndrome subtype is the deletion of the long arm of chromosome 5, giving with morphological features the diagnosis of myelodysplastic syndrome with isolated del(5q). These patients show a good prognosis and respond to treatment such as lenalidomide, but some cases progress to acute myeloid leukemia. However, the molecular mutation pattern is rarely characterized. Therefore, we investigated a large cohort of 123 myelodysplastic syndrome patients with isolated del(5q) diagnosed following the World Health Organization classifications 2008 and 2016 by sequencing 27 genes...
June 22, 2017: Haematologica
https://www.readbyqxmd.com/read/28636844/clonal-hematopoiesis-and-risk-of-atherosclerotic-cardiovascular-disease
#15
Siddhartha Jaiswal, Pradeep Natarajan, Alexander J Silver, Christopher J Gibson, Alexander G Bick, Eugenia Shvartz, Marie McConkey, Namrata Gupta, Stacey Gabriel, Diego Ardissino, Usman Baber, Roxana Mehran, Valentin Fuster, John Danesh, Philippe Frossard, Danish Saleheen, Olle Melander, Galina K Sukhova, Donna Neuberg, Peter Libby, Sekar Kathiresan, Benjamin L Ebert
BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP), which is defined as the presence of an expanded somatic blood-cell clone in persons without other hematologic abnormalities, is common among older persons and is associated with an increased risk of hematologic cancer. We previously found preliminary evidence for an association between CHIP and atherosclerotic cardiovascular disease, but the nature of this association was unclear. METHODS: We used whole-exome sequencing to detect the presence of CHIP in peripheral-blood cells and associated such presence with coronary heart disease using samples from four case-control studies that together enrolled 4726 participants with coronary heart disease and 3529 controls...
July 13, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28634614/detection-of-the-circulating-tumor-dnas-in-angioimmunoblastic-t-cell-lymphoma
#16
Mamiko Sakata-Yanagimoto, Rie Nakamoto-Matsubara, Daisuke Komori, Tran B Nguyen, Keiichiro Hattori, Toru Nanmoku, Takayasu Kato, Naoki Kurita, Yasuhisa Yokoyama, Naoshi Obara, Yuichi Hasegawa, Atsushi Shinagawa, Shigeru Chiba
Recent genetic studies identified that the disease-specific G17V RHOA mutation, together with mutations in TET2, DNMT3A, and IDH2, is a hallmark of angioimmunoblastic T cell lymphomas (AITL). The diagnostic value of these mutations is now being investigated. Circulating tumor DNAs (ctDNAs) may offer a non-invasive testing for diagnosis and disease monitoring of cancers. To investigate whether these mutations are useful markers for ctDNAs in AITL and its related lymphomas, we performed targeted sequencing for TET2, RHOA, DNMT3A, and IDH2 in paired tumors and cell-free DNAs from 14 patients at diagnosis...
June 20, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28634182/sf3b1-initiating-mutations-in-mds-with-ring-sideroblasts-target-lymphomyeloid-hematopoietic-stem-cells
#17
Teresa Mortera-Blanco, Marios Dimitriou, Petter S Woll, Mohsen Karimi, Edda Elvarsdottir, Simona Conte, Magnus Tobiasson, Monika Jansson, Iyadh Douagi, Matahi Moarii, Leonie Saft, Elli Papaemmanuil, Sten Eirik W Jacobsen, Eva Hellström-Lindberg
Mutations in the RNA splicing gene SF3B1 are found in more than 80% of patients with myelodysplastic syndrome with ring sideroblasts (MDS-RS). We investigated the origin of SF3B1 mutations within the bone marrow hematopoietic stem and progenitor cell compartments in patients with MDS-RS. Screening for recurrently mutated genes in the mononuclear cell fraction revealed mutations in SF3B1 in 39 of 40 cases (97.5%), combined with TET2 and DNMT3A in 11 (28%) and 6 (15%) patients, respectively. All recurrent mutations identified in mononuclear cells could be tracked back to the phenotypically defined hematopoietic stem cell (HSC) compartment in all investigated patients, and were also present in downstream myeloid and erythroid progenitor cells...
June 20, 2017: Blood
https://www.readbyqxmd.com/read/28626218/molecular-characterization-of-ezh2-mutant-patients-with-myelodysplastic-myeloproliferative-neoplasms
#18
J Rinke, J P Müller, M F Blaess, A Chase, M Meggendorfer, V Schäfer, N Winkelmann, C Haferlach, N C P Cross, A Hochhaus, T Ernst
Mutations in the epigenetic regulator gene EZH2 are frequently observed in patients with myelodysplastic/myeloproliferative neoplasms (MDS/MPN; 10-13%) and are associated with a poor outcome. To gain more insight into EZH2 pathology, we sought to genetically characterize a cohort of 41 EZH2-mutated MDS/MPN patients using targeted deep next-generation sequencing (NGS), colony-forming progenitor assays and transcriptome analysis. Stable short hairpin RNA (shRNA)-mediated downregulation of EZH2 was performed in MDS-derived F-36P, MOLM-13 and OCI-M2 cells to study EZH2-specific changes...
June 19, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28616099/epigenetic-silencing-of-sall3-is-an-independent-predictor-of-poor-survival-in-head-and-neck-cancer
#19
Kiyoshi Misawa, Daiki Mochizuki, Atsushi Imai, Yuki Misawa, Shiori Endo, Masato Mima, Hideya Kawasaki, Thomas E Carey, Takeharu Kanazawa
BACKGROUND: This study examined Sal-like protein (SALL)3 methylation profiles of head and neck cancer (HNSCC) patients at diagnosis and follow-up and evaluated their prognostic significance and value as a biomarker. SALL3 expression was examined in a panel of cell lines by quantitative reverse transcription polymerase chain reaction (RT-PCR). The methylation status of the SALL3 promoter was examined by quantitative methylation-specific PCR. RESULTS: SALL3 promoter methylation was associated with transcriptional inhibition and was correlated with disease recurrence in 64...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28608921/whole-exome-sequencing-reveals-critical-genes-underlying-metastasis-in-oesophageal-squamous-cell-carcinoma
#20
Wei Dai, Josephine Mun Yee Ko, Sheyne Sta Ana Choi, Zhouyou Yu, Luwen Ning, Hong Zheng, Vinod Gopalan, Kin Tak Chan, Nikki Pui-Yue Lee, Kwok Wah Chan, Simon Ying-Kit Law, Alfred King-Yin Lam, Maria Li Lung
Oesophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers, owing to a high frequency of metastasis. However, little is known about the genomic landscape of metastatic ESCC. To identify the genetic alterations that underlie ESCC metastasis, whole-exome sequencing was performed for 41 primary tumours and 15 lymph nodes (LNs) with metastatic ESCCs. Eleven cases included matched primary tumours, synchronous LN metastases, and non-neoplastic mucosa. Approximately 50-76% of the mutations identified in primary tumours appeared in the synchronous LN metastases...
June 13, 2017: Journal of Pathology
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