Somatic mutation theories

The somatic mutation theory of carcinogenesis states that mutation of DNA within somatic cells is required for neoplasia. The major pieces of evidence supporting the somatic mutation theory of carcinogenesis are shown in Table 24.4. 

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Fahmy, O.G. Fahmy, M.J. (1970) Gene elimination in carcinogenesis reinterpretation of the somatic mutation theory. Cancer Res., 30, 195-205... 

The concept that cancer involves an alteration in the genetic material of a somatic cell (somatic mutation theory) was first introduced by Theodor Boveri in 1914. Boveri suggested that cancer was related to chromosome abnormalities in somatic cells. With respect to chemical carcinogenesis, James and Elizabeth Miller in the 1950 s and 1960s observed that a wide variety of structurally diverse chemicals could produce cancer in laboratory animals. They suggested that many of these diverse... 

The somatic mutation theory is based, in part, on the idea that background radiation and/or various endogenous mutagens produce random chromosome damage in all cells. Over time, the genetic loci become sufficiently altered such that various critical functions fail and the cell dies. The fact that irradiation of laboratory animals results in accelerated aging and premature death lends some support to this hypothesis. However, since irradiation produces free radicals, it could be considered part of that theory. 

In view of the apparent relationship between chromosomal damage, mutagenesis and carcinogenesis [8-10], analyses of induced chromosomal aberrations have become a useful tool to evaluate potential hazards of environmental or occupational mutagens and carcinogens. The underlying premise, inherent in somatic mutation theory of cancer, is that an elevated frequency of chromosomal aberrations would increase the likelihood of the rearrangements that contribute to neoplastic transformation [11-13]. 

Somatic mutation theories (2,3,10-15) postulate that the origin of diversity is a normal genetic event (mutation, deletion, insertion or recombination) which occurs in V genes at low frequency throughout the life of the individual. We will first consider mechanisms that do not involve recombination. 

It should be noted that the existence of the a locus allotypes on Vh regions presents no major obstacle to the somatic mutation theory. 

Another difficulty arising from the somatic mutation theory concerns the conservation of allotypic determinants in rabbit Vh regions. Certain positions must be incapable of mutation to account for the presence of allotypic markers controlled by the a, x, or y loci on all or nearly all rabbit H chains. 

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