GENETICS OF SOMATIC CELLS 445 



by their tendency to grow in multiple layers rather than in monolayer. Thus, it seems 

 that the same phenotypic end result, the invasive cell, can be reached through one 

 single step of change or through a series of multiple steps. This is also true for some 

 other types of progression : one of the progression rules of Foulds 401 actually stresses 

 the existence of alternative paths of development. In his words: "One lesion 

 may develop in several different ways by direct paths or by indirect paths traversing 

 intermediate stages or precursor lesions. Progression may consist of steplike advances 

 along one path of development, or it may bring about a decisive change of path." 

 In genetics, it is almost a commonplace that mutants of identical or highly similar 

 phenotype may result from changes at quite different loci; and roughly similar end 

 effects may be caused by disturbances at any of the steps along a biosynthetic path- 

 way. 1173 Thus, no specific type of etiology such as serial mutations or viral oncogenesis 

 is necessary as the exclusive cause of a certain cellular phenotype, such as the invasive 

 cell with altered surface properties. 



Other phenotypic markers studied in neoplastic cells in vivo. — Many other characteristics 

 have been studied in tumor cells in vivo that are potentially useful as phenotypic markers 

 although very few have been actually employed in experiments aimed directly at the 

 selection of distinct sublines with different marker characteristics. The work of Hessel- 

 bach 553 is of interest. She showed that both pigmented and nonpigmented tumors 

 could be derived from a melanoma in mice by selective transfer of pigmented and non- 

 pigmented tissue, respectively. Genetic factors controlling host melanization did not 

 have any effect on the melanization of the tumor cells borne by the host; pigmentation 

 appeared to depend on the inherent properties of the tumor cells themselves. 



Another interesting phenotypic property is the ability of plasma-cell tumors to 

 produce individually distinctive abnormal proteins, both in mice 332 and men. 1032 

 In mice, transplanted plasma-cell neoplasms maintained their individual character- 

 istics through repeated generations of transfer. 332 Although they had been derived 

 from the same type of cell within the same inbred strain of mice, these lines of tumors 

 were not equivalent, and their protein products could be clearly differentiated. Al- 

 though the nature of these proteins and their relationship to the normal serum proteins 

 is not clear, it is tempting to seek a relationship to antibodies, presumably produced by 

 normal plasma cells. If there is such a relationship, there is a striking resemblance 

 between the fact that different malignant lines of plasma cells produce individually 

 specific substances and the postulate, inherent in the recently developed clonal selection 

 theories of antibody formation, 149, 772, 1308 that the precursors of the antibody-forming 

 cells should show a high degree of genetic diversity, arising from a high spontaneous 

 mutation rate, and that each cell spontaneously produces small amounts of the anti- 

 body corresponding to its own genotype. Mature cells are expected to proliferate 

 extensively under antigenic stimulation and produce large clones of cells genetically 

 preadapted to produce homologous antibody. The analogy between antibody forma- 

 tion and the appearance of abnormal proteins in plasma-cell tumors must not be 

 pursued too far at the present time, but if such an analogy exists, experimental plasma- 



