Genetic mutations oncogenic

As previously mentioned, the genetic mutations leading to the diseases that we call cancer can be stimulated by a variety of chemical, environmental, and viral triggers. Both RNA retroviruses and DNA viruses have been implicated in human cancer causation (Table 42.5), although many more DNA than RNA viruses have oncogenic potential (12,13). 

Spritz, R. A., Holmes, S. A., Ramesar, R., Greenberg, J., Curtis, D., and Beighton, P. (1992). Mutations of the KIT (mast/stem cell growth factor receptor) proto-oncogene account for a continuous range of phenotypes in human piebaldism. Am. J. Hum. Genet. 51 1058-1065. 

Sequential mutations within colonic epithelium result in cellular replication or enhanced invasiveness. Genetic changes include mutational activation of oncogenes and inactivation of tumor suppressor genes. 

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.

As in cancer predisposing syndromes, these genetic alterations are sometimes carried in the germline. Among human tumours, heritable mutations are an exception. Most alterations are acquired in somatic life in the form of chromosomal translocations, deletions, inversions, amplifications or point mutations. Certain oncogenic viruses play important roles in a few human tumours. Examples are human papilloma-virus in cervical cancer and skin tumours, Ep-stein-Barr virus in nasopharyngeal carcinoma and Burkitt s lymphoma, and human T-cell leukaemia viruses (e.g. HTLV-I, HTLV-II) in T-cell leukaemia. 

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