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Encyclopedia > Knudson hypothesis

The Knudson 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, [1][2] and later formulated by Alfred G. Knudson in 1971.[3] Knudson's work led indirectly to the identification of cancer-related genes. Knudson won the 1998 Albert Lasker Medical Research Award for this work. Look up Hypothesis in Wiktionary, the free dictionary. ... Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these cells to invade other tissues, either by direct growth into adjacent tissue through invasion, or by implantation into distant sites by metastasis. ... In biology, mutations are changes to the base pair sequence of genetic material (either DNA or RNA). ... The structure of part of a DNA double helix. ... Carl O. Nordling (b. ... 1953 (MCMLIII) was a common year starting on Thursday. ... Dr Alfred G. Knudson Jr. ... 1971 (MCMLXXI) was a common year starting on Friday (the link is to a full 1971 calendar). ... For other meanings of this term, see gene (disambiguation). ... The Albert Lasker Medical Research Award is one of a series of awards presented annually by the Lasker Foundation. ...

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 explaned by assuming that the outbreak of cancer requires the accumulations of six consecutive mutations. The British Journal of Cancer a twice-monthly professional medical journal of Cancer Research UK (a registered charity in the United Kingdom), published on their behalf by the Nature Publishing Group (a division of Macmillan Publishers Ltd). ...

Later, Knudson performed a statistical analysis on cases of retinoblastoma, a tumour of the retina which occurred both on children as a hereditary disease and in adults in a sporadic fashion. In addition, the children often developed the tumour in both eyes, suggesting an underlying predisposition. // Retinoblastoma is a cancer of the retina. ... Human eye cross-sectional view. ... For other uses, see Child (disambiguation). ... A genetic disorder, or genetic disease, is a condition caused by abnormal expression of one or more genes resulting in a clinical phenotype. ...

The findings were that multiple "hits" to DNA were necessary to cause cancer. In the children with retinoblastoma, the first insult was congenital, and any second insult would rapidly lead to cancer. In adult cases, two "hits" had to take place before a tumour could develop, explaining the age difference.

It was later found that carcinogenesis (the development of malignancy) depended both on the activation of oncogenes (genes that stimulate cell proliferation) and deactivation of tumor suppressor genes (genes that keep proliferation in check). A first "hit" in an oncogene would not necessarily lead to cancer, as normally functioning tumor suppressor genes (TSGs) would still counterbalance this impetus; only damage to TSGs would lead to unchecked proliferation. Conversely, a damaged TSG (such as the Rb1 gene in retinoblastoma) would not lead to cancer unless there is a growth impetus from an activated oncogene. Cancers are caused by a series of mutations. ... An oncogene is a modified gene that increases the malignancy of a tumor cell. ... A tumor suppressor gene is a gene that reduces the probability that a cell in a multicellular organism will turn into a tumor cell. ...

Field cancerisation may be an extended form of the Knudson hypothesis. This is the phenomenon of various primary tumours developing in one particular area of the body, suggesting that an earlier "hit" predisposed the whole area for malignancy.


  1. ^ Nordling C (1953). "A new theory on cancer-inducing mechanism". Br J Cancer 7 (1): 68-72. PMID 13051507.
  2. ^ Marte B (2006-04-01). Milestone 9: (1953) Two-hit hypothesis - It takes (at least) two to tango. Nature Milestones Cancer. Retrieved on 2007-01-22.
  3. ^ Knudson A (1971). "Mutation and cancer: statistical study of retinoblastoma". Proc Natl Acad Sci U S A 68 (4): 820-3. PMID 5279523.

This article or section does not cite its references or sources. ... January 22 is the 22nd day of the year in the Gregorian calendar. ... The Proceedings of the National Academy of Sciences (USA), mostly commonly referred to as PNAS, is the official publication of the National Academy of Sciences of the United States of America. ...

External Links

  • [http://www-ermm.cbcu.cam.ac.uk/01002678h.htm Knudsonā€™s two-hit hypothesis for tumouri

  Results from FactBites:
Scientific Reports (7972 words)
In a professional setting, the hypothesis might have something to do with how cells react to a certain kind of genetic manipulation, but the purpose of the experiment is to learn more about potential cancer treatments.
In a solubility experiment, for example, your hypothesis might talk about the relationship between temperature and the rate of solubility, but the purpose is probably to learn more about some specific scientific principle underlying the process of solubility.
As a result, you may want to say that the hypothesis was "proved" or "disproved," or that it was "correct" or "incorrect." These terms, however, reflect a degree of certainty that you as a scientist aren't supposed to have.
  More results at FactBites »



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