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Genetics of Cancer We often talk about cancer as if it were a single disease at a single site ... o but it is a complex series of diseases that share a common problem ... o 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 o The proto-oncogenes normally push the cell forward through the cell cycle Tumor-suppressor genes normally act as brakes in the cell cycle o In the case of the tumor-suppressor genes, some individuals may inherit a defective allele but not develop cancer because they are heterozygous o However, they are predisposed to cancer due to loss of heterozygosity for the tumor-suppressor gene o One of the most important tumor-suppressor genes is the p53 gene o 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 o This can lead to general genomic instability o 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