Download The Genetics of Cancer

Genetics of Cancer
 We often talk about cancer as if it were a single disease at a single site ...
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but it is a complex series of diseases that share a common problem ...
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uncontrolled cell division
Cancer vocabulary
 When tumor cells remain localized, the tumor is benign
 If the cells invade other body tissues, the tumor is malignant
 If the cells have caused tumors at other body sites, this is metastasis
 So they just keep dividing
 But in order to do so, they have to ignore the usual checkpoints in the cell cycle
 But that’s not the only odd property of cancer cells
Cancer genetics
 1971 - Alfred Knudson proposed that the development of cancer is a multistep
process requiring at least two mutations
 This explained why cancer can be inherited or can occur spontaneously
Cancer genes
 Oncogenes arise from mutations in proto-oncogenes
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The proto-oncogenes normally push the cell forward through the cell
cycle
 Tumor-suppressor genes normally act as brakes in the cell cycle
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In the case of the tumor-suppressor genes, some individuals may inherit a
defective allele but not develop cancer because they are heterozygous
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However, they are predisposed to cancer due to loss of heterozygosity for
the tumor-suppressor gene
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One of the most important tumor-suppressor genes is the p53 gene
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The role of pRB is known
 Translocations can create new genes by fusing parts of two genes together
 Translocations can also cause position effects leading to inappropriate expression
patterns for genes
o Changes in chromosome number and/or structure are often seen in cancers
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This can lead to general genomic instability
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Cascade effect
o Viruses have also been implicated in cancers
o The progression of cancer is dependent on a progression of mutations
o The progression leads to more aggressive forms of the cancer