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TET2
Tet methylcytosine dioxygenase 2 (''TET2'') is a human gene. It resides at chromosome 4q24, in a region showing recurrent microdeletions and copy-neutral loss of heterozygosity (CN-LOH) in patients with diverse myeloid malignancies. Function ''TET2'' encodes a protein that catalysis, catalyzes the conversion of the modified DNA base methylcytosine to 5-hydroxymethylcytosine. The first mechanistic reports showed tissue-specific accumulation of 5-Hydroxymethylcytosine, 5-hydroxymethylcytosine (5-Hydroxymethylcytosine, 5hmC) and the conversion of 5-Methylcytosine, 5mC to 5-Hydroxymethylcytosine, 5hmC by Tet methylcytosine dioxygenase 1, TET1 in humans in 2009. In these two papers, Kriaucionis and Heintz provided evidence that a high abundance of 5hmC can be found in specific tissues and Tahiliani et al. demonstrated the Tet methylcytosine dioxygenase 1, TET1-dependent conversion of 5-Methylcytosine, 5mC to 5-Hydroxymethylcytosine, 5hmC. A role for TET1 in cancer was reported in ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
DNA Demethylation
For molecular biology in mammals, DNA demethylation causes replacement of 5-methylcytosine (5mC) in a DNA sequence by cytosine (C) (see figure of 5mC and C). DNA demethylation can occur by an active process at the site of a 5mC in a DNA sequence or, in replicating cells, by preventing addition of methyl groups to DNA so that the replicated DNA will largely have cytosine in the DNA sequence (5mC will be diluted out). Methylated cytosine is frequently present in the linear DNA sequence where a cytosine is followed by a guanine in a Directionality (molecular biology), 5' → 3' direction (a CpG site). In mammals, DNA methyltransferases (which add methyl groups to DNA bases) exhibit a strong sequence preference for cytosines at CpG sites. There appear to be more than 20 million CpG dinucleotides in the human genome (see CpG site#Genomic distribution, genomic distribution). In mammals, on average, 70% to 80% of CpG cytosines are methylated, though the level of methylation varies with ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Acute Myeloid Leukaemia
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may include feeling tired, shortness of breath, easy bruising and bleeding, and increased risk of infection. Occasionally, spread may occur to the brain, skin, or gums. As an acute leukemia, AML progresses rapidly, and is typically fatal within weeks or months if left untreated. Risk factors include getting older, being male, smoking, previous chemotherapy or radiation therapy, myelodysplastic syndrome, and exposure to the chemical benzene. The underlying mechanism involves replacement of normal bone marrow with leukemia cells, which results in a drop in red blood cells, platelets, and normal white blood cells. Diagnosis is generally based on bone marrow aspiration and specific blood tests. AML has several subtypes for which treatments and ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Base Excision Repair
Base excision repair (BER) is a cellular mechanism, studied in the fields of biochemistry and genetics, that repairs damaged DNA throughout the cell cycle. It is responsible primarily for removing small, non-helix-distorting base lesions from the genome. The related nucleotide excision repair pathway repairs bulky helix-distorting lesions. BER is important for removing damaged bases that could otherwise cause mutations by mispairing or lead to breaks in DNA during replication. BER is initiated by DNA glycosylases, which recognize and remove specific damaged or inappropriate bases, forming AP sites. These are then cleaved by an AP endonuclease. The resulting single-strand break can then be processed by either short-patch (where a single nucleotide is replaced) or long-patch BER (where 2–10 new nucleotides are synthesized). Lesions processed by BER Single bases in DNA can be chemically damaged by a variety of mechanisms, the most common ones being deamination, oxidation, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Chronic Myelomonocytic Leukaemia
Chronic myelomonocytic leukemia (CMML) is a type of leukemia, which are cancers of the blood-forming cells of the bone marrow. In adults, blood cells are formed in the bone marrow, by a process that is known as haematopoiesis. In CMML, there are increased numbers of monocytes and immature blood cells ( blasts) in the peripheral blood and bone marrow, as well as abnormal looking cells (dysplasia) in at least one type of blood cell. CMML shows characteristics of a myelodysplastic syndrome (MDS); a disorder that produces abnormal looking blood cells, and a myeloproliferative neoplasm (MPN); a disorder characterised by the overproduction of blood cells. For this reason, CMML was reclassified as a MDS/MPN overlap disorder in 2002. For a diagnosis of CMML, the World Health Organization (WHO) states that the blood monocyte count must be >1 billion/L, no Philadelphia chromosome or mutations in the PDGFRA or PDGFRB gene should be present, the blast count must be 10% and 1 billion/L is essent ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Myeloproliferative Neoplasms
Myeloproliferative neoplasms (MPNs) are a group of rare blood cancers in which excess red blood cells, white blood cells or platelets are produced in the bone marrow. ''Myelo'' refers to the bone marrow, ''proliferative'' describes the rapid growth of blood cells and ''neoplasm'' describes that growth as abnormal and uncontrolled. The overproduction of blood cells is often associated with a somatic mutation, for example in the JAK2, CALR, TET2, and MPL gene markers. In rare cases, some MPNs such as primary myelofibrosis may accelerate and turn into acute myeloid leukemia. Classification MPNs are classified as blood cancers by most institutions and organizations. In MPNs, the neoplasm (abnormal growth) starts out as benign and can later become malignant. As of 2016, the World Health Organization lists the following subcategories of MPNs: * Chronic myeloid leukemia (CML) * Chronic neutrophilic leukemia (CNL) * Polycythemia vera (PV) * Primary myelofibrosis (PMF) ** PMF, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
5-Methylcytosine
5-Methylcytosine (5mC) is a methylation, methylated form of the DNA base cytosine (C) that regulates gene Transcription (genetics), transcription and takes several other biological roles. When cytosine is methylated, the DNA maintains the same sequence, but the Gene expression#DNA methylation and demethylation in transcriptional regulation, expression of methylated genes can be altered (the study of this is part of the field of epigenetics). 5-Methylcytosine is incorporated in the nucleoside 5-Methylcytidine, 5-methylcytidine. Discovery While trying to isolate the bacterial toxin responsible for tuberculosis, W.G. Ruppel isolated a novel nucleic acid named tuberculinic acid in 1898 from ''Mycobacterium tuberculosis, Tubercle bacillus''. The nucleic acid was found to be unusual, in that it contained in addition to thymine, guanine and cytosine, a methylated nucleotide. In 1925, Treat Baldwin Johnson, Johnson and Coghill successfully detected a minor amount of a methylated cytosi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tet Methylcytosine Dioxygenase 1
Ten-eleven translocation methylcytosine dioxygenase 1 (TET1) is a member of the TET family of enzymes, in humans it is encoded by the TET1 gene. Its function, regulation, and utilizable pathways remain a matter of current research while it seems to be involved in DNA demethylation and therefore gene regulation, but is expressed as different isoforms which may have distinct functions. Discovery TET1 was first discovered in a 61-year-old patient with a rare variation of t(10;11)(q22;q23) acute myeloid leukemia (AML) as a zinc-finger binding protein (specifically on the CXXC domain) that fuses to the gene MLL. Another study confirmed that this protein was a translocation partner of MLL in an 8-year-old patient with t(10;11)(q22;q23) AML and named the protein Ten-Eleven Translocation 1. Function TET1 catalyzes the conversion of the modified DNA base 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC). : TET1 produces 5-hmC by oxidation of 5-mC in an iron and al ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Demethylation
Demethylation is the chemical process resulting in the removal of a methyl group (CH3) from a molecule. A common way of demethylation is the replacement of a methyl group by a hydrogen atom, resulting in a net loss of one carbon and two hydrogen atoms. The counterpart of demethylation is methylation. In biochemistry : Demethylation is relevant to epigenetics. Demethylation of DNA is catalyst, catalyzed by demethylases. These enzymes oxidize N-methyl groups, which occur in histones, in lysine derivatives, and in some forms of DNA. :R2N-CH3 + O → R2N-H + CH2O One family of such oxidative enzymes is the cytochrome P450. Alpha-ketoglutarate-dependent hydroxylases are also active for demethylation of DNA, operating by a similar stoichiometry. These reactions, which proceed via hydroxylation, exploit the slightly weakened Carbon–hydrogen bond, C-H bonds of methylamines and methyl ethers. Demethylation of some sterols are steps in the biosynthesis of testosterone and ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Zygosity
Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Most eukaryotes have two matching sets of chromosomes; that is, they are diploid. Diploid organisms have the same locus (genetics), loci on each of their two sets of homologous chromosomes except that the sequences at these loci may differ between the two chromosomes in a matching pair and that a few chromosomes may be mismatched as part of a chromosomal Sex-determination system#Chromosomal determination, sex-determination system. If both alleles of a diploid organism are the same, the organism is #Homozygous, homozygous at that locus. If they are different, the organism is #Heterozygous, heterozygous at that locus. If one allele is missing, it is #Hemizygous, hemizygous, and, if both alleles are missing, it is #Nullizygous, nullizygous. The ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Myelodysplastic Syndrome
A myelodysplastic syndrome (MDS) is one of a group of cancers in which blood cells in the bone marrow do not mature, and as a result, do not develop into healthy blood cells. Early on, no symptoms typically are seen. Later, symptoms may include fatigue, shortness of breath, bleeding disorders, anemia, or frequent infections. Some types may develop into acute myeloid leukemia. Risk factors include previous chemotherapy or radiation therapy, exposure to certain chemicals such as tobacco smoke, pesticides, and benzene, and exposure to heavy metals such as Mercury (element), mercury or lead. Problems with blood cell formation result in some combination of low anemia, red blood cell, thrombocytopenia, platelet, and white blood cell counts. Some types of MDS cause an increase in the production of immature blood cells (called blast cell, blasts), in the bone marrow or peripheral blood, blood. The different types of MDS are identified based on the specific characteristics of the chang ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Somatic Evolution In Cancer
Somatic evolution is the accumulation of mutations and Epigenetic clock, epimutations in somatic cells (the cells of a body, as opposed to germ plasm and stem cells) during a lifetime, and the effects of those mutations and Cancer epigenetics, epimutations on the Fitness (biology), fitness of those cells. This evolutionary process has first been shown by the studies of Bert Vogelstein in colon cancer. Somatic evolution is important in the process of aging as well as the development of some diseases, including cancer. Natural selection in cancer Cells in pre-malignant and Neoplasm#Malignant neoplasms, malignant neoplasms (tumors) evolve by natural selection. This accounts for how cancer develops from normal tissue and why it has been difficult to cure. There are three necessary and sufficient conditions for natural selection, all of which are met in a neoplasm: # There must be Tumour heterogeneity, variation in the population. Neoplasms are mosaics of different mutant cells with both ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Chromatin
Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in reinforcing the DNA during cell division, preventing DNA repair#DNA damage, DNA damage, and regulating gene expression and DNA replication. During mitosis and meiosis, chromatin facilitates proper segregation of the chromosomes in anaphase; the characteristic shapes of chromosomes visible during this stage are the result of DNA being coiled into highly condensed chromatin. The primary protein components of chromatin are histones. An octamer of two sets of four histone cores (Histone H2A, Histone H2B, Histone H3, and Histone H4) bind to DNA and function as "anchors" around which the strands are wound.Maeshima, K., Ide, S., & Babokhov, M. (2019). Dynamic chromatin organization without the 30 nm fiber. ''Current opinion in cell biolog ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
