A genome mutation in three related sublines of the Ehrlich-Lettré mouse ascites tumor1,2

Granzow, Christof; Nielsén, Karin

doi:10.1111/j.1601-5223.1984.tb00110.x

Cited by 9 publications

(1 citation statement)

References 35 publications

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“…The currently prevailing theory of Nowell (Science, 1976) holds that unexplained “genetic instability” generates “variant sublines (with) changes in chromosome number” and that “clonal” progressions arise by “stepwise selection of more aggressive sublines” [ 14 ]. The literature, however, contains numerous examples of selections of “immediate” progressions [ 14 ] with multiple new chromosomes [ 7 , 15 – 18 ] - notably experimentally initiated fusions between cancers and heterologous cells [ 18 – 26 ]. Furthermore, the prevailing stepwise theory predicts stable intermediate sublines of cancers with multiple non-clonal additions of new chromosomes.…”

Section: Introductionmentioning

confidence: 99%

Is cancer progression caused by gradual or simultaneous acquisitions of new chromosomes?

Bloomfield

Duesberg

2018

Mol Cytogenet

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BackgroundFoulds defined, “Tumor progression (as a) permanent, irreversible qualitative change in one or more of its characters” (Cancer Res. 1954). Accordingly progressions, such as metastases and acquired drug-resistance, were since found to be subspecies of cancers with conserved and numerous new chromosomes. Here we ask whether cancers acquire numerous new chromosomes gradually or simultaneously in progressions. The currently prevailing theory of Nowell (Science, 1976) holds that unexplained “genetic instability” generates “variant sublines (with) changes in chromosome number” and that “clonal” progressions arise by “stepwise selection of more aggressive sublines”. The literature, however, contains many examples of “immediate” selections of progressions with numerous new chromosomes - notably experimentally initiated fusions between cancers and heterologous cells. Furthermore, the stepwise progression theory predicts intermediate sublines of cancers with multiple non-clonal additions of new chromosomes. However, the literature does not describe such intermediates.ResultsIn view of these inconsistencies with stepwise progression we test here a saltational theory, in which the inherent variability of cancer-specific aneuploidy generates “immediate” progressions with individual clonal karyotypes, transcriptomes and phenotypes in single steps. Using cell fusion as an established controllable model of “immediate” progression, we generated seven immortal murine hybridomas by fusing immortal murine myeloma cells and normal antibody-producing B-cells with polyethylene glycol within a few minutes. These immortal hybridomas contained individual sets of 71 to 105 clonal chromosomes, compared to the 52 chromosomes of the parental myeloma. Thus the myeloma had gained 19 to 53 new clonal chromosomes in seven individual hybridomas in a single step. Furthermore, no stable intermediates were found, as would be predicted by a saltational process.ConclusionsWe conclude that random fusions between myelomas and normal B-cells generate clonal hybridomas with multiple, individual chromosomes in single steps. Similar single-step mechanisms may also generate the “late” clonal progressions of cancers with gains of numerous new chromosomes and thus explain the absence of intermediates. Latency would reflect the low probability of rare stochastic progressions. In conclusion, the karyotypic clonality of hybridomas and spontaneous progressions suggests karyotypic alterations as proximate causes of neoplastic progressions. Since cancer-specific aneuploidy catalyzes karyotypic variation, the degree of aneuploidy predicts the clinical risk of neoplastic progression, confirming classical predictions based on DNA content.

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Section: Introductionmentioning

confidence: 99%

Is cancer progression caused by gradual or simultaneous acquisitions of new chromosomes?

Bloomfield

Duesberg

2018

Mol Cytogenet

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Comparative study of nuclear and cytoplasmic glycogen isolated from mutant HD33 ascites cells

Kopun¹,

Granzow²,

Krisman³

1989

J of Cellular Biochemistry

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Mutant cells of the HD33 subline of the Ehrlich-Lettré ascites tumor synthesize and store glycogen mainly intranuclearly, when growing in vivo, and exclusively in the cytoplasm, when permanently cultivated as a suspension cell strain. To investigate whether there exist differences between glycogen of nuclear and cytoplasmic origin, the ultrastructure and the biophysical and biochemical properties of glycogen from in vivo and in vitro grown HD33 ascites cells were compared. Pronounced heterogeneity and differences in glycogen particle ultrastructure were evident in situ and after isolation of the native, high-molecular polysaccharide. Nuclear glycogen contains a fraction of heavier molecules (up to 2 X 10(9)) and larger particles (up to 340 nm) which could not be found in the cytoplasmic preparations, which contained only particles smaller than 140 nm. The subparticles of beta-type are similar in both nuclear and cytoplasmic glycogen. The absorption spectra and glucose analysis after degradation with phosphorylase and debranching enzyme indicate that nuclear glycogen has a higher degree of branching, associated with a decrease in the average chain length between the branching points, and shorter external polyglucosidic chains than cytoplasmic glycogen. This is the first report about the analysis and properties of isolated nuclear glycogen.

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Difference in cell surface 5'-nucleotidase activity, protein iodination and membrane properties between mouse lymphoma and rat adenocarcinoma cell variants with low and high-metastatic potential

Haeffner

Doenges

Buchholz

1988

International Journal of Biochemistry

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A genome mutation in three related sublines of the Ehrlich-Lettré mouse ascites tumor1,2

Cited by 9 publications

References 35 publications

Is cancer progression caused by gradual or simultaneous acquisitions of new chromosomes?

Is cancer progression caused by gradual or simultaneous acquisitions of new chromosomes?

Comparative study of nuclear and cytoplasmic glycogen isolated from mutant HD33 ascites cells

Difference in cell surface 5'-nucleotidase activity, protein iodination and membrane properties between mouse lymphoma and rat adenocarcinoma cell variants with low and high-metastatic potential

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