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Malignant Transformation
Malignant transformation is the process by which cells acquire the properties of cancer. This may occur as a primary process in normal tissue, or secondarily as ''malignant degeneration'' of a previously existing benign tumor. Causes There are many causes of primary malignant transformation, or tumorigenesis. Most human cancers in the United States are caused by external factors, and these factors are largely avoidable. These factors were summarized by Doll and Peto in 1981, and were still considered to be valid in 2015. These factors are listed in the table. a Reproductive and sexual behaviors include: number of partners; age at first menstruation; zero versus one or more live births Examples of diet-related malignant transformation Diet and colon cancer Colon cancer provides one example of the mechanisms by which diet, the top factor listed in the table, is an external factor in cancer. The Western diet of African Americans in the United States is associated with a y ...
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Transformation (genetics)
In molecular biology and genetics, transformation is the genetic alteration of a cell resulting from the direct uptake and incorporation of exogenous genetic material from its surroundings through the cell membrane(s). For transformation to take place, the recipient bacterium must be in a state of competence, which might occur in nature as a time-limited response to environmental conditions such as starvation and cell density, and may also be induced in a laboratory. Transformation is one of three processes that lead to horizontal gene transfer, in which exogenous genetic material passes from one bacterium to another, the other two being conjugation (transfer of genetic material between two bacterial cells in direct contact) and transduction (injection of foreign DNA by a bacteriophage virus into the host bacterium). In transformation, the genetic material passes through the intervening medium, and uptake is completely dependent on the recipient bacterium. As of 2014 abou ...
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Regulation Of Transcription In Cancer
Generally, in progression to cancer, hundreds of genes are silenced or activated. Although silencing of some genes in cancers occurs by mutation, a large proportion of carcinogenic gene silencing is a result of altered DNA methylation (see DNA methylation in cancer). DNA methylation causing silencing in cancer typically occurs at multiple CpG sites in the CpG islands that are present in the promoters of protein coding genes. Altered expressions of microRNAs also silence or activate many genes in progression to cancer (see microRNAs in cancer). Altered microRNA expression occurs through hyper/hypo-methylation of CpG sites in CpG islands in promoters controlling transcription of the microRNAs. Silencing of DNA repair genes through methylation of CpG islands in their promoters appears to be especially important in progression to cancer (see methylation of DNA repair genes in cancer). CpG islands in promoters In humans, about 70% of promoters located near the transcription star ...
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Cancer Epigenetics
Cancer epigenetics is the study of epigenetic modifications to the DNA of cancer cells that do not involve a change in the nucleotide sequence, but instead involve a change in the way the genetic code is expressed. Epigenetic mechanisms are necessary to maintain normal sequences of tissue specific gene expression and are crucial for normal development. They may be just as important, if not even more important, than genetic mutations in a cell's transformation to cancer. The disturbance of epigenetic processes in cancers, can lead to a loss of expression of genes that occurs about 10 times more frequently by transcription silencing (caused by epigenetic promoter hypermethylation of CpG islands) than by mutations. As Vogelstein et al. points out, in a colorectal cancer there are usually about 3 to 6 driver mutations and 33 to 66 hitchhiker or passenger mutations. However, in colon tumors compared to adjacent normal-appearing colonic mucosa, there are about 600 to 800 heavily methylat ...
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Noncoding DNA
Non-coding DNA (ncDNA) sequences are components of an organism's DNA that do not encode protein sequences. Some non-coding DNA is transcribed into functional non-coding RNA molecules (e.g. transfer RNA, microRNA, piRNA, ribosomal RNA, and regulatory RNAs). Other functional regions of the non-coding DNA fraction include regulatory sequences that control gene expression; scaffold attachment regions; origins of DNA replication; centromeres; and telomeres. Some non-coding regions appear to be mostly nonfunctional such as introns, pseudogenes, intergenic DNA, and fragments of transposons and viruses. Fraction of non-coding genomic DNA In bacteria, the coding regions typically take up 88 % of the genome. The remaining 12 % consists largely of non-coding genes and regulatory sequences, which means that almost all of the bacterial genome has a function. The amount of coding DNA in eukaryrotes is usually a much smaller fraction of the genome because eukaryotic genom ...
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Genome Instability
Genome instability (also genetic instability or genomic instability) refers to a high frequency of mutations within the genome of a cellular lineage. These mutations can include changes in nucleic acid sequences, chromosomal rearrangements or aneuploidy. Genome instability does occur in bacteria. In multicellular organisms genome instability is central to carcinogenesis, and in humans it is also a factor in some neurodegenerative diseases such as amyotrophic lateral sclerosis or the neuromuscular disease myotonic dystrophy. The sources of genome instability have only recently begun to be elucidated. A high frequency of externally caused DNA damage can be one source of genome instability since DNA damage can cause inaccurate translesion DNA synthesis past the damage or errors in repair, leading to mutation. Another source of genome instability may be epigenetic or mutational reductions in expression of DNA repair genes. Because endogenous (metabolically-caused) DNA damage is ve ...
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Exome
The exome is composed of all of the exons within the genome, the sequences which, when transcribed, remain within the mature RNA after introns are removed by RNA splicing. This includes untranslated regions of messenger RNA (mRNA), and coding regions. Exome sequencing has proven to be an efficient method of determining the genetic basis of more than two dozen Mendelian or single gene disorders. Statistics The human exome consists of roughly 233,785 exons, about 80% of which are less than 200 base pairs in length, constituting a total of about 1.1% of the total genome, or about 30 megabases of DNA. Though composing a very small fraction of the genome, mutations in the exome are thought to harbor 85% of mutations that have a large effect on disease. Definition It is important to note that the exome is distinct from the transcriptome, which is all of the transcribed RNA within a cell type. While the exome is constant from cell-type to cell-type, the transcriptome changes bas ...
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Somatic (biology)
The term somatic - etymologically from the Ancient Greek words of "σωματικός" (sōmatikós, “bodily”) and σῶμα (sôma, “body”) - is often used in biology to refer to the cells of the body in contrast to the reproductive ( germline) cells, which usually give rise to the egg or sperm (or other gametes in other organisms). These somatic cells are diploid, containing two copies of each chromosome, whereas germ cells are haploid, as they only contain one copy of each chromosome (in preparation for fertilisation). Although under normal circumstances all somatic cells in an organism contain identical DNA, they develop a variety of tissue-specific characteristics. This process is called differentiation, through epigenetic and regulatory alterations. The grouping of similar cells and tissues creates the foundation for organs. Somatic mutations are changes to the genetics of a multicellular organism that are not passed on to its offspring through the germline. ...
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Helicobacter Pylori
''Helicobacter pylori'', previously known as ''Campylobacter pylori'', is a gram-negative, microaerophilic, spiral (helical) bacterium usually found in the stomach. Its helical shape (from which the genus name, helicobacter, derives) is thought to have evolved in order to penetrate the mucoid lining of the stomach and thereby establish infection. The bacterium was first identified in 1982 by the Australian doctors Barry Marshall and Robin Warren. ''H. pylori'' has been associated with cancer of the mucosa-associated lymphoid tissue in the stomach, esophagus, colon, rectum, or tissues around the eye (termed extranodal marginal zone B-cell lymphoma of the cited organ), and of lymphoid tissue in the stomach (termed diffuse large B-cell lymphoma). ''H. pylori'' infection usually has no symptoms but sometimes causes gastritis (stomach inflammation) or ulcers of the stomach or first part of the small intestine. The infection is also associated with the development of ...
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Human Papillomaviruses
Human papillomavirus infection (HPV infection) is caused by a DNA virus from the '' Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and results in either warts or precancerous lesions. These lesions, depending on the site affected, increase the risk of cancer of the cervix, vulva, vagina, penis, anus, mouth, tonsils, or throat. Nearly all cervical cancer is due to HPV and two strains – HPV16 and HPV18 – account for 70% of cases. HPV16 is responsible for almost 90% of HPV-positive oropharyngeal cancers. Between 60% and 90% of the other cancers listed above are also linked to HPV. HPV6 and HPV11 are common causes of genital warts and laryngeal papillomatosis. An HPV infection is caused by ''human papillomavirus'', a DNA virus from the papillomavirus family. Over 170 types have been described. An individual can become infected with more than one type of HPV, and the di ...
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Merkel Cell Polyomavirus
Merkel cell polyomavirus (MCV or MCPyV) was first described in January 2008 in Pittsburgh, Pennsylvania. It was the first example of a human viral pathogen discovered using unbiased metagenomic next-generation sequencing with a technique called digital transcriptome subtraction. MCV is one of seven currently known human oncoviruses. It is suspected to cause the majority of cases of Merkel cell carcinoma, a rare but aggressive form of skin cancer. Approximately 80% of Merkel cell carcinoma (MCC) tumors have been found to be infected with MCV. MCV appears to be a common—if not universal—infection of older children and adults. It is found in respiratory secretions suggesting that it may be transmitted by a respiratory route. But it also can be found shedding from healthy skin, and in gastrointestinal tract tissues and elsewhere, and so its precise mode of transmission remains unknown. In addition, recent studies suggest that this virus may latently infect the human sera and ...
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Human T-lymphotrophic Virus
The human T-lymphotropic virus, human T-cell lymphotropic virus, or human T-cell leukemia-lymphoma virus (HTLV) family of viruses are a group of human retroviruses that are known to cause a type of cancer called adult T-cell leukemia/lymphoma and a demyelinating disease called HTLV-1 associated myelopathy/tropical spastic paraparesis ( HAM/TSP). The HTLVs belong to a larger group of primate T-lymphotropic viruses (PTLVs). Members of this family that infect humans are called HTLVs, and the ones that infect Old World monkeys are called Simian T-lymphotropic viruses (STLVs). To date, four types of HTLVs ( HTLV-1, HTLV-2, HTLV-3, and HTLV-4) and four types of STLVs (STLV-1, STLV-2, STLV-3, and STLV-5) have been identified. HTLV types HTLV-1 and HTLV-2 viruses are the first retroviruses discovered. Both belong to the oncovirus subfamily of retroviruses and can transform human lymphocytes so that they are self-sustaining in vitro. The HTLVs are believed to originate from interspecie ...
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