Double Minute
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Double Minute
Double minutes are small fragments of extrachromosomal DNA, which have been observed in a large number of human tumors including breast, lung, ovary, colon, and most notably, neuroblastoma. They are a manifestation of gene amplification as a result of chromothripsis, during the development of tumors, which give the cells selective advantages for growth and survival. This selective advantage is as a result of double minutes frequently harboring amplified oncogenes and genes involved in drug resistance. DMs, like actual chromosomes, are composed of chromatin and replicate in the nucleus of the cell during cell division. Unlike typical chromosomes, they are composed of circular fragments of DNA, up to only a few million base pairs in size, and contain no centromere or telomere. Further to this, they often lack key regulatory elements, allowing genes to be constitutively expressed. The term ecDNA may be used to refer to DMs in a more general manner. Formation The most commonl ...
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Extrachromosomal DNA
Extrachromosomal DNA (abbreviated ecDNA) is any DNA that is found off the chromosomes, either inside or outside the nucleus of a cell. Most DNA in an individual genome is found in chromosomes contained in the nucleus. Multiple forms of extrachromosomal DNA exist, and, while some of these serve important biological functions, they can also play a role in diseases, such as ecDNA in cancer. In prokaryotes, nonviral extrachromosomal DNA is primarily found in plasmids, whereas, in eukaryotes extrachromosomal DNA is primarily found in organelles. Mitochondrial DNA is a main source of this extrachromosomal DNA in eukaryotes. The fact that this organelle contains its own DNA supports the hypothesis that mitochondria originated as bacterial cells engulfed by ancestral eukaryotic cells. Extrachromosomal DNA are often used in research of replication because they are easy to identify and isolate. Although extrachromosomal circular DNA (eccDNA) is found in normal eukaryotic cells, extrachro ...
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Regulatory Element
A regulatory sequence is a segment of a nucleic acid molecule which is capable of increasing or decreasing the expression of specific genes within an organism. Regulation of gene expression is an essential feature of all living organisms and viruses. Description In DNA, regulation of gene expression normally happens at the level of RNA biosynthesis (transcription). It is accomplished through the sequence-specific binding of proteins (transcription factors) that activate or inhibit transcription. Transcription factors may act as activators, repressors, or both. Repressors often act by preventing RNA polymerase from forming a productive complex with the transcriptional initiation region ( promoter), while activators facilitate formation of a productive complex. Furthermore, DNA motifs have been shown to be predictive of epigenomic modifications, suggesting that transcription factors play a role in regulating the epigenome. In RNA, regulation may occur at the level of prot ...
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Acute Myeloid Leukemia
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 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 outcomes may vary. T ...
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Malignancy
Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not self-limited in its growth, is capable of invading into adjacent tissues, and may be capable of spreading to distant tissues. A benign tumor has none of those properties. Malignancy in cancers is characterized by anaplasia, invasiveness, and metastasis. Malignant tumors are also characterized by genome instability, so that cancers, as assessed by whole genome sequencing, frequently have between 10,000 and 100,000 mutations in their entire genomes. Cancers usually show tumour heterogeneity, containing multiple subclones. They also frequently have reduced expression of DNA repair enzymes due to epigenetic methylation of DNA repair genes or altered microRNAs that control DNA repair gene expression. Tumours can be detected through the visual ...
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Chromatid
A chromatid (Greek ''khrōmat-'' 'color' + ''-id'') is one half of a duplicated chromosome. Before replication, one chromosome is composed of one DNA molecule. In replication, the DNA molecule is copied, and the two molecules are known as chromatids. During the later stages of cell division these chromatids separate longitudinally to become individual chromosomes. Chromatid pairs are normally genetically identical, and said to be homozygous. However, if mutations occur, they will present slight differences, in which case they are heterozygous. The pairing of chromatids should not be confused with the ploidy of an organism, which is the number of homologous versions of a chromosome. Sister chromatids Chromatids may be sister or non-sister chromatids. A sister chromatid is either one of the two chromatids of the same chromosome joined together by a common centromere. A pair of sister chromatids is called a dyad. Once sister chromatids have separated (during the anaphase of ...
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Breakage-fusion-bridge Cycle
Breakage-fusion-bridge (BFB) cycle (also breakage-rejoining-bridge cycle) is a mechanism of chromosomal instability, discovered by Barbara McClintock in the late 1930s. Mechanism The BFB cycle begins when the end region of a chromosome, called its telomere, breaks off. When that chromosome subsequently replicates it forms two sister chromatids which both lack a telomere. Since telomeres appear at the end of chromatids, and function to prevent their ends from fusing with other chromatids, the lack of a telomere on these two sister chromatids causes them to fuse with one another. During anaphase the sister chromatids will form a bridge where the centromere in one of the sister chromatids will be pulled in one direction of the dividing cell, while the centromere of the other will be pulled in the opposite direction. Being pulled in opposite directions will cause the two sister chromatids to break apart from each other, but not necessarily at the site that they fused. This results in t ...
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DNA Methylation
DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts to repress gene transcription. In mammals, DNA methylation is essential for normal development and is associated with a number of key processes including genomic imprinting, X-chromosome inactivation, repression of transposable elements, aging, and carcinogenesis. As of 2016, two nucleobases have been found on which natural, enzymatic DNA methylation takes place: adenine and cytosine. The modified bases are N6-methyladenineD. B. Dunn, J. D. Smith: ''The occurrence of 6-methylaminopurine in deoxyribonucleic acids.'' In: ''Biochem J.'' 68(4), Apr 1958, S. 627–636. PMID 13522672. ., 5-methylcytosineB. F. Vanyushin, S. G. Tkacheva, A. N. Belozersky: ''Rare bases in animal DNA.'' In: ''Nature.'' 225, 1970, S. 948–949. PMID 4391887. and N4 ...
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Chromosomal Fragile Site
A chromosomal fragile site is a specific heritable point on a chromosome that tends to form a gap or constriction and may tend to break when the cell is exposed to partial replication stress. Based on their frequency, fragile sites are classified as "common" or "rare". To date, more than 120 fragile sites have been identified in the human genome. Common fragile sites are considered part of normal chromosome structure and are present in all (or nearly all) individuals in a population. Under normal conditions, most common fragile sites are not prone to spontaneous breaks. Common fragile sites are of interest in cancer studies because they are frequently affected in cancer and they can be found in healthy individuals. Sites FRA3B (harboring the ''FHIT'' gene) and FRA16D (harboring the ''WWOX'' gene) are two well known examples and have been a major focus of research. Rare fragile sites are found in less than 5% of the population, and are often composed of two- or three-nucleotide rep ...
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Hypoxia (medical)
Hypoxia is a condition in which the body or a region of the body is deprived of adequate oxygen supply at the tissue level. Hypoxia may be classified as either '' generalized'', affecting the whole body, or ''local'', affecting a region of the body. Although hypoxia is often a pathological condition, variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise.. Hypoxia differs from hypoxemia and anoxemia, in that hypoxia refers to a state in which oxygen present in a tissue or the whole body is insufficient, whereas hypoxemia and anoxemia refer specifically to states that have low or no oxygen in the blood. Hypoxia in which there is complete absence of oxygen supply is referred to as anoxia. Hypoxia can be due to external causes, when the breathing gas is hypoxic, or internal causes, such as reduced effectiveness of gas transfer in the lungs, reduced capacity of the blood to carry oxygen, compromised gene ...
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Homogeneously Staining Region
Homogeneously staining regions (HSRs) are chromosomal segments with various lengths and uniform staining intensity after G banding. This type of aberration is also known as Copy Number Gains or Amplification. An HSR is one type of change in a chromosome's structure which is frequently observed in the nucleus of human cancer cells. In the region of a chromosome where an HSR occurs, a segment of the chromosome, which presumably contains a gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ... or genes that give selective advantage to the progression of the cancer, is amplified or duplicated many times. As a result of the duplication this chromosomal segment is greatly lengthened and expanded such that when it is stained with a fluorescent probe specific to the region ( Fluorescent ...
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Amplicon
In molecular biology, an amplicon is a piece of DNA or RNA that is the source and/or product of amplification or replication events. It can be formed artificially, using various methods including polymerase chain reactions (PCR) or ligase chain reactions (LCR), or naturally through gene duplication. In this context, ''amplification'' refers to the production of one or more copies of a genetic fragment or target sequence, specifically the amplicon. As it refers to the product of an amplification reaction, ''amplicon'' is used interchangeably with common laboratory terms, such as "PCR product." Artificial amplification is used in research, forensics, and medicine for purposes that include detection and quantification of infectious agents, identification of human remains, and extracting genotypes from human hair. Natural gene duplication plays a major role in evolution. It is also implicated in several forms of human cancer including primary mediastinal B cell lymphoma and Ho ...
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Chromosomal Translocation
In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes balanced and unbalanced translocation, with two main types: reciprocal-, and Robertsonian translocation. Reciprocal translocation is a chromosome abnormality caused by exchange of parts between non-homologous chromosomes. Two detached fragments of two different chromosomes are switched. Robertsonian translocation occurs when two non-homologous chromosomes get attached, meaning that given two healthy pairs of chromosomes, one of each pair "sticks" and blends together homogeneously. A gene fusion may be created when the translocation joins two otherwise-separated genes. It is detected on cytogenetics or a karyotype of affected cells. Translocations can be balanced (in an even exchange of material with no genetic information extra or missing, and ideally full functionality) or unbalanced (where the exchange of chromosome material is unequal resulting in extr ...
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