Karyotype alteration generates the neoplastic phenotypes of SV40-infected XXXX and rodent cells.

@entity1 @entity778 @entity2007 @entity5 @entity19 @entity35 @entity105
BACKGROUND: Despite over 50  years of research, it remains unclear how the DNA @entity5 viruses SV40 and Polyoma cause @entity5 . Prevailing theories hold that virus-coded @entity5 ( @entity5 )-antigens cause @entity5 by inactivating cellular @entity5 suppressor genes. But these theories don't explain four characteristics of @entity105 : (1) less than one in 10,000 infected cells become @entity5 cells, (2) @entity5 have complex individual phenotypes and transcriptomes, (3) recurrent @entity5 without viral DNA and proteins, (4) preneoplastic aneuploidies and immortal neoplastic clones with individual karyotypes. RESULTS: As an alternative theory we propose that @entity105 is a form of speciation, initiated by virus-induced @entity2007 . Since @entity2007 destabilizes the karyotype by unbalancing thousands of genes it catalyzes chain reactions of karyotypic and transcriptomic evolutions. Eventually rare karyotypes evolve that encode @entity5 -specific autonomy of growth. The low probability of forming new @entity5 -species by random karyotypic and transcriptomic variations predicts @entity5 . Although @entity5 karyotypes are congenitally aneuploid and thus variable, they are stabilized or immortalized by selections for variants with @entity5 -specific autonomy. Owing to these inherent variations @entity5 karyotypes are heterogeneous within clonal margins. To test this theory we analyzed karyotypes and phenotypes of SV40-infected @entity1 , @entity35 and @entity19 cells developing into neoplastic clones. In all three systems we found (1) preneoplastic @entity5 with individual clonal but flexible karyotypes and phenotypes, which arose from less than one in 10,000 infected cells, survived over 200 generations, but were either @entity5 -antigen positive or negative, (3) spontaneous and drug-induced variations of neoplastic phenotypes correlating 1-to-1 with karyotypic variations. CONCLUSIONS: Since all 14 virus-induced neoplastic clones tested contained individual clonal karyotypes and phenotypes, we conclude that these karyotypes have generated and since maintained these neoplastic clones. Thus SV40 causes @entity5 indirectly, like carcinogens, by inducing @entity2007 from which new @entity5 -specific karyotypes evolve automatically at low rates. This theory explains the (1) low probability of carcinogenesis per @entity778 cell, (2) the individuality and clonal flexibility of @entity5 karyotypes, (3) recurrence of @entity5 without viral @entity5 -antigens, and (4) the individual clonal karyotypes, transcriptomes and immortality of virus-induced @entity5 - all unexplained by current viral theories.
