The proposed origin of double minutes from Homogeneously Staining Region (HSR)-marker chromosomes in human neuroblastoma hybrid cell lines

Balaban-Malenbaum, Gloria; Gilbert, Fiona J.

doi:10.1016/0165-4608(80)90065-5

Cited by 46 publications

(7 citation statements)

References 20 publications

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“…3C Chromosomally amplified CAD genes do not produce CAD episomes. Previous studies proposed that chromosomally amplified sequences may recombine to generate extrachromosomal sequences (3). We could test this possibility by using this system, since the PALA-resistant cell line T5S1-3 has a 50-fold chromosomal amplification of the donated CAD gene tandem array, and CAD episomes can be fractionated away from chromosomal DNA.…”

Section: Resultsmentioning

confidence: 99%

Double minute chromosomes can be produced from precursors derived from a chromosomal deletion.

et al. 1988

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Recent experiments have shown that gene amplification can be mediated by submicroscopic, autonomously replicating, circular extrachromosomal molecules. We refer to those molecules as episomes (S. Carroll, P. Gaudray, M. L. DeRose, J. F. Emery, J. L. Meinkoth, E. Nakkim, M. Subler, D. D. Von Hoff, and G. M. Wahl, Mol. Cell. Biol. 7:1740-1750. The experiments reported in this paper explore the way episomes are formed and their fate in the cell over time. The data reveal that in our system the episomes are initially 250 kilobases, but gradually enlarge until they become double minute chromosomes. In addition, we show that episomes or double minute chromosomes can integrate into chromosomes. Our results also suggest that episomes can be produced by deletion of the corresponding sequences from the chromosome.

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Section: Resultsmentioning

confidence: 99%

Double minute chromosomes can be produced from precursors derived from a chromosomal deletion.

et al. 1988

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“…Cytological manifestations of gene amplification include expanded chromosome regions which band abnormally by the trypsin-Giemsa method, called homogeneously staining regions (HSRs) (74,75), extraehromosomal paired chromatin fragments (double minutes, DMs) (76)(77)(78) and abnormally banded regions (ABRs) (79,80). As will be discussed later, several lines of evidence suggest that HSRs, DMs and ABRs represent interchangeable forms of gene amplification (81,82,79).…”

Section: Increased Ploidy Levels and Chromosome Aberrations In Highlymentioning

confidence: 99%

“…It has been suggested that HSRs, DMs and ABRs may interconvert reciprocally, being the intrachromosomal lesions (HSRs and ABRs) more stable than the extrachromosomal ones (DMs). HSRs break down to form DMs in hybrids between human cells with HSRs only and mouse cells containing a selectable phenotype (82).…”

Section: The Role Of Proto-oncogene And/or Oncogene Amplification In mentioning

confidence: 99%

Somatic cell fusion as a source of genetic rearrangement leading to metastatic variants

Larizza

Schirrmacher

1984

Cancer Metast Rev

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Tumor cell populations displaying metastatic properties often have higher gene dosage than their less malignant progenitor tumors, as shown by increased ploidy levels, chromosome duplication and gene amplification. The acquisition by tumor cells of high chromosome numbers may be due to endoreduplication or somatic hybridization either between tumor cells or between tumor and host cells. All such mechanisms increase genetic variability and instability in tumor cells since they trigger a polyploidization-segregation cycle. Among the wide variety of segregants which may emerge from high-ploidy cells, variants with increased malignancy can be positively selected in vivo. Evidence for in vivo fusion of tumor and normal host cells has been reported in different tumor systems. However the attainment by tumor-host hybrids of a higher degree of malignancy has only been observed following substantial chromosome segregation. The involvement of a cell of bone marrow origin as preferential host partner in the fusion process has been proved both by studies on tumor-host hybrids in bone marrow radiation chimeras and in vitro hybridization experiments between non-metastatic tumors and normal lymphoreticular cells which have led to the establishment of metastatic variants. Several different segregational mechanisms may bring about homozygosity or hemizygosity of recessive alleles in tumor-host hybrids, leading to their expression. The marked chromosome dynamics of tumor-host hybrids are also responsible for extensive chromosome rearrangements. At the molecular level these may represent mechanisms causing altered oncogene activity. The activation of new oncogenes by transposition or amplification as well as the amplification of previously activated oncogenes are the mechanisms most likely to be responsible for transition from low to high malignancy, occurring through ploidy changes, such as those produced by somatic mating.

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“…1969;Urlaubct al" 1981). In another example, cell hybrids formed between human neuro blastoma cells containing an HSR structure and a normal mouse line without an HSR resulted in hy brids in which the HSR had disappeared and DM structures were now present in the metaphase spreads (Balaban-Malenbaum and Gilbert, 1980). Further more, Wigley and Cowell (1984) described an in traspecific mouse hybrid cell clone in which the HSR present in one parent was absent in about half the cell population and was replaced by DM structures.…”

Section: Discussionmentioning

confidence: 99%

Destabilization of the adenosine deaminase gene sequences in rat-rat somatic cell hybrids

Hoffee¹,

Chiang²,

Rowland³

1987

Cytogenet Genome Res

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Rat hepatoma cells amplified for adenosine deaminase (ADA) gene sequences show the amplified DNA on large, homogeneously staining regions (HSRs). The amplified cells are stable in the absence of selection for 12 mo without loss of ADA activity or gene sequences. However, in hybrids formed between an amplified cell line with a prominent HSR and a nonamplified cell line, rapid loss of ADA activity, as well as gene sequences, occurs. Karyotype analyses of the hybrids indicate that the HSR structures are no longer visible in a large percentage of the hybrid metaphase spreads and appear to have been replaced by DNA structures that resemble double minutes. Our data provide evidence that (1) the extent of the breakdown of the HSR in the hybrids may be affected by the presence of an active adenosine kinase or the level of ATP in the cells and (2) additional unidentified factors are present in the hybrids that affect the integrity of the HSR structure. There is no evidence for a specific transacting factor in nonamplified cells that regulates gene amplification.

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The proposed origin of double minutes from Homogeneously Staining Region (HSR)-marker chromosomes in human neuroblastoma hybrid cell lines

Cited by 46 publications

References 20 publications

Double minute chromosomes can be produced from precursors derived from a chromosomal deletion.

Double minute chromosomes can be produced from precursors derived from a chromosomal deletion.

Somatic cell fusion as a source of genetic rearrangement leading to metastatic variants

Destabilization of the adenosine deaminase gene sequences in rat-rat somatic cell hybrids

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