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- Q387059 subject Q8343806.
- Q387059 abstract "The Knudson hypothesis, also known as the two-hit hypothesis or multiple-hit hypothesis, is the hypothesis that cancer is the result of accumulated mutations to a cell's DNA. It was first proposed by Carl O. Nordling in 1953, and later formulated by Alfred G. Knudson in 1971. Knudson's work led indirectly to the identification of cancer-related genes. Knudson won the 1998 Albert Lasker Clinical Medical Research Award for this work.The multi-mutation theory on cancer was proposed by Nordling in the British Journal of Cancer in 1953. He noted that in industrialized nations the frequency of cancer seems to increase according to the sixth power of age. This correlation could be explained by assuming that the outbreak of cancer requires the accumulations of six consecutive mutations.Later, Knudson performed a statistical analysis on cases of retinoblastoma, a tumor of the retina that occurs both as an inherited disease and sporadically. He noted that inherited retinoblastoma occurs at a younger age than the sporadic disease. In addition, the children with inherited retinoblastoma often developed the tumor in both eyes, suggesting an underlying predisposition.Knudson suggested that multiple "hits" to DNA were necessary to cause cancer. In the children with inherited retinoblastoma, the first insult was inherited in the DNA, and any second insult would rapidly lead to cancer. In non-inherited retinoblastoma, two "hits" had to take place before a tumor could develop, explaining the age difference.It was later found that carcinogenesis (the development of cancer) depended both on the activation of proto-oncogenes (genes that stimulate cell proliferation) and on the deactivation of tumor suppressor genes (TSG), which are genes that keep proliferation in check. Knudson's hypothesis refers specifically, however, to the heterozygosity of tumor suppressor genes. A mutation in both alleles is required, as a single functional TSG is sufficient.".
- Q387059 wikiPageWikiLink Q1087765.
- Q387059 wikiPageWikiLink Q12078.
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- Q387059 wikiPageWikiLink Q136696.
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- Q387059 wikiPageWikiLink Q41719.
- Q387059 wikiPageWikiLink Q422445.
- Q387059 wikiPageWikiLink Q42918.
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- Q387059 wikiPageWikiLink Q7187.
- Q387059 wikiPageWikiLink Q7430.
- Q387059 wikiPageWikiLink Q8343806.
- Q387059 comment "The Knudson hypothesis, also known as the two-hit hypothesis or multiple-hit hypothesis, is the hypothesis that cancer is the result of accumulated mutations to a cell's DNA. It was first proposed by Carl O. Nordling in 1953, and later formulated by Alfred G. Knudson in 1971. Knudson's work led indirectly to the identification of cancer-related genes.".
- Q387059 label "Knudson hypothesis".