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Oncogene
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==History== The theory of oncogenes was foreshadowed by the German biologist [[Theodor Boveri]] in his 1914 book ''Zur Frage der Entstehung Maligner Tumoren'' (Concerning the Origin of Malignant Tumors) in which he predicted the existence of oncogenes ''(Teilungsfoerdernde Chromosomen)'' that become amplified ''(im permanenten Übergewicht)'' during tumor development.<ref>{{cite book | vauthors = Boveri T |title=Zur Frage der Entstehung maligner Tumoren |date=1914 |publisher=Gustav Fischer |location=Jena}}</ref> Later on, the term "oncogene" was rediscovered in 1969 by [[National Cancer Institute]] scientists George Todaro and [[Robert Huebner]].<ref>[[The Emperor of All Maladies]], Siddhartha Mukherjee, 2011, p. 363</ref> The first confirmed oncogene was discovered in 1970 and was termed [[Proto-oncogene tyrosine-protein kinase Src|SRC]] (pronounced "sarc" as it is short for sarcoma). SRC was first discovered as an oncogene in a chicken [[retrovirus]]. Experiments performed by Dr. G. Steve Martin of the [[University of California, Berkeley]] demonstrated that SRC was indeed the gene of the virus that acted as an oncogene upon infection.<ref name="pmid11389470">{{cite journal | vauthors = Martin GS | title = The hunting of the Src | journal = Nature Reviews. Molecular Cell Biology | volume = 2 | issue = 6 | pages = 467–475 | date = June 2001 | pmid = 11389470 | doi = 10.1038/35073094 | s2cid = 205016442 }}</ref> The first [[nucleic acid sequence|nucleotide sequence]] of [[v-Src]] was [[DNA sequencing|sequenced]] in 1980 by A.P. Czernilofsky et al.<ref name="pmid6253794">{{cite journal | vauthors = Czernilofsky AP, Levinson AD, Varmus HE, Bishop JM, Tischer E, Goodman HM | title = Nucleotide sequence of an avian sarcoma virus oncogene (src) and proposed amino acid sequence for gene product | journal = Nature | volume = 287 | issue = 5779 | pages = 198–203 | date = September 1980 | pmid = 6253794 | doi = 10.1038/287198a0 | s2cid = 4231060 | bibcode = 1980Natur.287..198C }}</ref> In 1976, Drs. {{ill|Dominique Stéhelin|fr}}, [[J. Michael Bishop]] and [[Harold E. Varmus]] of the [[University of California, San Francisco]] demonstrated that oncogenes were activated proto-oncogenes as is found in many organisms, including humans. Bishop and Varmus were awarded the [[Nobel Prize in Physiology or Medicine]] in 1989 for their discovery of the cellular origin of retroviral oncogenes.<ref>[http://nobelprize.org/nobel_prizes/medicine/laureates/1989/press.html Nobel Prize in Physiology or Medicine for 1989 jointly to J. Michael Bishop and Harold E. Varmus for their discovery of "the cellular origin of retroviral oncogenes".] Press Release.</ref> Dr. [[Robert Weinberg (biologist)|Robert Weinberg]] is credited with discovering the first identified human oncogene in a human [[bladder cancer]] cell line.<ref>{{cite journal | vauthors = Shih C, Weinberg RA | title = Isolation of a transforming sequence from a human bladder carcinoma cell line | journal = Cell | volume = 29 | issue = 1 | pages = 161–169 | date = May 1982 | pmid = 6286138 | doi = 10.1016/0092-8674(82)90100-3 | s2cid = 12046552 }}</ref><ref>{{cite news | vauthors = Lowry F |title=Robert Weinberg Rewarded for Oncogene Discovery |url=https://www.medscape.com/viewarticle/742131 |access-date=6 February 2020 |work=Medscape |date=5 May 2011}}</ref> The molecular nature of the mutation leading to oncogenesis was subsequently isolated and characterized by the Spanish biochemist [[Mariano Barbacid]] and published in ''[[Nature (journal)|Nature]]'' in 1982.<ref name="T24">{{cite journal | vauthors = Reddy EP, Reynolds RK, Santos E, Barbacid M | title = A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene | journal = Nature | volume = 300 | issue = 5888 | pages = 149–152 | date = November 1982 | pmid = 7133135 | doi = 10.1038/300149a0 | s2cid = 34599264 | bibcode = 1982Natur.300..149R }}</ref> Dr. Barbacid spent the following months extending his research, eventually discovering that the oncogene was a mutated [[allele]] of [[HRAS]] and characterizing its activation mechanism. The resultant protein encoded by an oncogene is termed '''oncoprotein'''.<ref name=Kumar20>{{cite book | chapter = Chapter 20 - Neoplasms of the Thyroid | vauthors = Mitchell RS, Kumar V, Abbas AK, Fausto N |title=Robbins Basic Pathology|publisher=Saunders |location=Philadelphia |isbn=978-1-4160-2973-1 |year=2007 | edition = 8th }}</ref> Oncogenes play an important role in the regulation or synthesis of proteins linked to tumorigenic cell growth. Some oncoproteins are accepted and used as tumor markers.
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