WikiDoc Resources for Knudson hypothesis Articles Most recent articles on Knudson hypothesis Most cited articles on Knudson hypothesis Review articles on Knudson hypothesis Articles on Knudson hypothesis in N Eng J Med, Lancet, BMJ Media Powerpoint slides on Knudson hypothesis Images of Knudson hypothesis Photos of Knudson hypothesis Podcasts & MP3s on Knudson hypothesis Videos on Knudson hypothesis Evidence Based Medicine Cochrane Collaboration on Knudson hypothesis Bandolier on Knudson hypothesis TRIP on Knudson hypothesis Clinical Trials Ongoing Trials on Knudson hypothesis at Clinical Trials.gov Trial results on Knudson hypothesis Clinical Trials on Knudson hypothesis at Google Guidelines / Policies / Govt US National Guidelines Clearinghouse on Knudson hypothesis NICE Guidance on Knudson hypothesis NHS PRODIGY Guidance FDA on Knudson hypothesis CDC on Knudson hypothesis Books Books on Knudson hypothesis News Knudson hypothesis in the news Be alerted to news on Knudson hypothesis News trends on Knudson hypothesis Commentary Blogs on Knudson hypothesis Definitions Definitions of Knudson hypothesis Patient Resources / Community Patient resources on Knudson hypothesis Discussion groups on Knudson hypothesis Patient Handouts on Knudson hypothesis Directions to Hospitals Treating Knudson hypothesis Risk calculators and risk factors for Knudson hypothesis Healthcare Provider Resources Symptoms of Knudson hypothesis Causes & Risk Factors for Knudson hypothesis Diagnostic studies for Knudson hypothesis Treatment of Knudson hypothesis Continuing Medical Education (CME) CME Programs on Knudson hypothesis International Knudson hypothesis en Espanol Knudson hypothesis en Francais Business Knudson hypothesis in the Marketplace Patents on Knudson hypothesis Experimental / Informatics List of terms related to Knudson hypothesis ## Overview[edit | edit source] 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. 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 tumour of the retina which 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 tumour 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 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. 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. ## References[edit | edit source] 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 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. ## External Links[edit | edit source] * Knudson’s two-hit hypothesis for tumourigenesis involving a tumour suppressor gene (TSG) Template:WikiDoc Sources