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The Cancer Journal - Volume 5, Number 5 (September-October 1992)

editorial


Chromosome-tissue interactions and morphogenesis



During a recent conference devoted to the theorical basis of carcinogenesis, a cytogeneticist gave an outstanding lecture on the incidence and specificity of chromosomal abnormalities in solid tumours. His talk left me, and I think the rest of his audience, in very little doubt as to the relationship between karyotypic modifications and the appearance of many solid tumours. Among the changes found in a given type of tumour are a change which is probably specific and a number of non-specific random changes. These random changes cannot be classified systematically and are usually thought to be epiphenomena. Let us accept this suggestion and concentrate on the relationship between two groups of observations: on one hand the structural changes in the tissue which lead histologists to a firm diagnosis of a malignant tumour, and on the other hand these chromosomal alterations which are more and more commonly considered to be specific. There is an undisputable relationship between these two sets of data. Althought the precise nature of the relationship between tissue morphology and chromosomal structure is not yet known, we are tempted to see the chromosomal changes as the effective cause, that is, the real physical cause, of the changes in the tissue. This is only a hypothesis. Howewer, it is a very strong hypothesis, as is shown by the difficulty of convincing some people that it is only a hypothesis. So, dear readers; can I imagine how difficult it will be for me to persuade you to accept the alternative hypothesis? That is, that tissue change could "hypothetically" be the cause of chromosomal changes. This is opposed to what we hear, what we see writen and what we believe to be true. Let us say, not that tissue alterations can induce alteration in chromosomes, but rather that tissue morphology and karyotype are interactive. Both are normal in healthy tissue and altered in tumours, by a number of dependent, bi-directionnal lesions. Today, it is easy to accept that the normal organized structure is the result of a dynamic equilibrium involving a large number of different cellular and extracellular factors. A lasting disturbance of this equilibrium can lead to hyperplasia, metaplasia or a tumour. There is no reason to suppose, now that we know about the plasticity of the genome, that the karyotype is not also the result of a dynamic equilibrium, stabe certainly, but also subject to disruption. Support for the hypothesis of the mutual dependence of tissue and chromosomal structures can be found in the frequent observation of karyotypic abnormalities associated with murine cells in culture.

The specificity of chromosomal abnormalities leads us to search for specific mechanisms. A deletion, that is a loss of genetic material, affecting the two autosomes, corresponding to the location of a powerful anti-oncogene, such as the retinoblastoma gene, strongly suggests a mechanism for carcinogenic transformation. Some translocations are associated with a known reorganization of the genome. However, the majority of the deletions and translocations thought to be specific have only been associated with structural changes; no explanatory biochemical mechanisms have been discovered. Here we are suggesting that we should admit the possibility of bi-directional relationships and try to devise experiments to support or refute this hypothesis. The conditions will necessarily be different from those currently employed to verify the hypothesis of a one-way mechanism of carcinogenesis in the complex system made up of the genome, chromosomes, cells and tissues.


Jean-Claude Salomon
e-mail: salomon@tribunes.com

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