Aneuploidy

Down syndrome patients, who have an extra Chromosome 21, are known to develop malignancies such as leukemia and testicular cancer, though the reasons for this difference are not well understood. Characteristic changes in the copy number of particular chromosomes and chromosomal segments are seen in acute myeloid leukemia. These changes are so well-defined that they are used for prognostication in acute myeloid leukemia.

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Translocations

 Translocations are characteristic changes in chromosomes where portions of the human genome exchange locations on different chromosomes. The most famous example of this is the Philadelphia chromosome, a translocation of chromosomes 9 and 22, which brings the genes [[bcr]] and [[abl]] in close apposition. The constitutive activation of the [[abl]] tyrosine kinase gene by [[bcr]] is known to give rise to chronic myeloid leukemia. The pharmaceutical product, Gleevec, targets the [[abl]] kinase and specifically inhibits that tyrosine kinase, leading to prolonged remissions in that disease.

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Biochemical explanations of cancer pathogenesis

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Malignant tumor cells have distinct properties:

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   * evading apoptosis

   * unlimited growth potential (immortalitization) due to overabundance of telomerase

   * self-sufficiency of growth factors

   * insensitivity to anti-growth factors

   * increased cell division rate

   * altered ability to differentiate

   * no ability for contact inhibition

   * ability to invade neighbouring tissues

   * ability to build metastases at distant sites

   * ability to promote blood vessel growth (angiogenesis)

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A cell that degenerates into a tumor cell does not usually acquire all these properties at once, but its descendent cells are selected to develop them. This process is called clonal evolution. A first step in the development of a tumor cell is usually a small change in the DNA, often a point mutation, which leads to a genetic instability of the cell. The instability can increase to a point where the cell loses whole chromosomes, or has multiple copies of several. Also, the DNA methylation pattern of the cell changes, activating and deactivating genes without the usual regulation. Cells that divide at a high rate, such as epithelial cells, show a higher risk of becoming tumor cells than those which divide less, for example neurons.