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Proliferation
Cell Cycle
Mutations
Euploidy
Polyploidy
Aneuploidy
Duesbergs/Rasnick Hypothesis
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You are here Background | Duesbergs/Rasnick Hypothesis
   

The two-hit theory of carcinogenesis of Alfred G. Knudsen

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Retinoblastoma, an eye cancer, is very rare in the general population, but common in retinoblastoma families

In view of this Knudsen hypothesized in 1971 that retinoblastoma is caused by two mutations, one of which must be inherited

The retinoblastoma-gene RB1, identified in 1986, then became the archetypal tumour suppressor gene
 
The theory of carcinogenesis by mutations of Bert Vogelstein
 
Vogelstein and Eric R. Fearon published in 1990
a model of sequential mutations of six genes that should lead
to colorectal cancer (along with Cristoph Lengauer,
and Martin Nowak)
One point mutation mostly results in only one abnormal protein
 
 
 
Visualisation of an Exon-22 point-mutation in the FANCD2 gene on chromosome 3 leading to Fanconi anemia. Affected patients suffer from cancer in early ages.
One point mutation mostly results in only one abnormal protein
 
 
The current somatic mutation-theory of carcinogenesis
 
 
Courtesy: National Cancer Institute, USA
“Cancer usually arises in a single cell. The cell’s progress from normal to malignant to metastatic appears to follow a series of distinct steps, each controlled by a different gene
or set of genes. Persons with a hereditary cancer already have the first mutation”.
 
 
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The birth of the mutation hypothesis
of carcinogenesis

 
 
 

 

 
 
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Do six mutations cause colorectal cancer?

 

 

 

 

 

 

 
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One human
chromosome
contains about
1.000 genes

 

 

 

 

 

 

 

 

 
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Mutations may cause cancer via chromosomal aneuploidy

 

 

 

 

 

 

 

 

     
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