Tumour genetic changes

Understanding cancer involves not only knowledge of the genetic changes that cause a normal cell to develop into a tumour cell but also the response of the whole body to a tumour, factors that increase or decrease the risk of development of a tumour and the current therapies that arrest growth of, or kill, tumour cells. These topics are discussed in this chapter, but some basic information is required first the cell cycle, the growth of a tissue, the fuels used by tumour cells and, finally, the role of genes. 

Andreassen, A., Vikse, R., Mikalsen, A., Adamovic, T., Steffensen, I.L., Hjerthohn, H., Levan, G., and Alexander, J. (2006) 2-Amino-l-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induces genetic changes in murine intestinal tumours and cells with ApcMin mutation. Mutat. Res. 604, 60-70. 

Figure 21.19 Development of a secondary carcinoma from a normal epithelium by effects of activated genes, i.e. oncogenes, and inactive tumour suppressor genes. It is somatic mutations in four or five genes in a given cell plus hypomethylation changes in histones and chromatin stracture that are involved. It is the accumulation of these genetic alterations, not the sequence, that determines the progression to a tumour cell.

When reinjected into fresh animals, isolated nucleic acids from polyoma virus particles caused tumours (see references cited in reference [35]). Coupled with the identification of other cancer nucleic acids, this suggests that a permanent change at the genetic centre of the cell is associated with cancer. However, this was thought to be associated only with a method of growth acceleration, rather than being relevant to initiation or promotion. 

As stated above, primary tumours and DTCs diverge genetically, not only for the number of aberrations, but also for their specific nature. This has been shown for copy number changes (Schmidt-Kittler et al. 2003 Stoecklein et al. 2008) and point mutations (Klein et al. 2002). 

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