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American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1984 Mar;36(2):387–397.

Werner's syndrome: proliferation in vitro of clones of cells bearing chromosome translocations.

S Schonberg, M F Niermeijer, D Bootsma, E Henderson, J German
PMCID: PMC1684414  PMID: 6324581

Abstract

Each of several cultures of Werner's syndrome (WS) fibroblasts and lymphoblasts examined was found to be composed of one or several clones of cells with mutated chromosome complements. Two "sister" fibroblasts cell lines (FCLs) that were derived from a mixture of explants cut from the same WS skin biopsy were found to have completely different rearranged chromosome complements. Daily observation of the skin explants from which these two sister FCLs were derived revealed not only that no more than a few fibroblasts ever migrated from a given explant but also that fibroblasts migrated from only a few of the explants. Two of three lymphoblastoid cell lines (LCLs), each probably developed as an independent clone from a different cell from the same WS blood sample, were mosaic, comprised of cells having both normal and rearranged chromosome complements. The third LCL studied, although nonmosaic, had a rearranged chromosome complement, but one that was completely different from those in the other two lines. Based on the observations described, hypotheses have been formulated to explain both the preponderance in long-term WS cultures of clones with mutated chromosome complements and the abbreviated lifespan characteristic of WS fibroblast cultures.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Chaganti R. S., Schonberg S., German J. A manyfold increase in sister chromatid exchanges in Bloom's syndrome lymphocytes. Proc Natl Acad Sci U S A. 1974 Nov;71(11):4508–4512. doi: 10.1073/pnas.71.11.4508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Epstein C. J., Martin G. M., Schultz A. L., Motulsky A. G. Werner's syndrome a review of its symptomatology, natural history, pathologic features, genetics and relationship to the natural aging process. Medicine (Baltimore) 1966 May;45(3):177–221. doi: 10.1097/00005792-196605000-00001. [DOI] [PubMed] [Google Scholar]
  3. Fujiwara Y., Higashikawa T., Tatsumi M. A retarded rate of DNA replication and normal level of DNA repair in Werner's syndrome fibroblasts in culture. J Cell Physiol. 1977 Sep;92(3):365–374. doi: 10.1002/jcp.1040920305. [DOI] [PubMed] [Google Scholar]
  4. Hand R., German J. A retarded rate of DNA chain growth in Bloom's syndrome. Proc Natl Acad Sci U S A. 1975 Feb;72(2):758–762. doi: 10.1073/pnas.72.2.758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Henderson E., Miller G., Robinson J., Heston L. Efficiency of transformation of lymphocytes by Epstein-Barr virus. Virology. 1977 Jan;76(1):152–163. doi: 10.1016/0042-6822(77)90292-6. [DOI] [PubMed] [Google Scholar]
  6. Hoehn H., Bryant E. M., Au K., Norwood T. H., Boman H., Martin G. M. Variegated translocation mosaicism in human skin fibroblast cultures. Cytogenet Cell Genet. 1975;15(5):282–298. doi: 10.1159/000130526. [DOI] [PubMed] [Google Scholar]
  7. Holliday R., Porterfield J. S., Gibbs D. D. Premature ageing and occurance of altered enzyme in Werner's syndrome fibroblasts. Nature. 1974 Apr 26;248(5451):762–763. doi: 10.1038/248762a0. [DOI] [PubMed] [Google Scholar]
  8. Martin G. M., Sprague C. A., Epstein C. J. Replicative life-span of cultivated human cells. Effects of donor's age, tissue, and genotype. Lab Invest. 1970 Jul;23(1):86–92. [PubMed] [Google Scholar]
  9. Nordenson I. Chromosome breaks in Werner's syndrome and their prevention in vitro by radical-scavenging enzymes. Hereditas. 1977;87(2):151–154. doi: 10.1111/j.1601-5223.1978.tb01256.x. [DOI] [PubMed] [Google Scholar]
  10. Norwood T. H., Hoehn H., Salk D., Martin G. M. Cellular aging in Werner's syndrome: a unique phenotype? J Invest Dermatol. 1979 Jul;73(1):92–96. doi: 10.1111/1523-1747.ep12532778. [DOI] [PubMed] [Google Scholar]
  11. Salk D., Au K., Hoehn H., Martin G. M. Cytogenetics of Werner's syndrome cultured skin fibroblasts: variegated translocation mosaicism. Cytogenet Cell Genet. 1981;30(2):92–107. doi: 10.1159/000131596. [DOI] [PubMed] [Google Scholar]
  12. Salk D., Au K., Hoehn H., Stenchever M. R., Martin G. M. Evidence of clonal attenuation, clonal succession, and clonal expansion in mass cultures of aging Werner's syndrome skin fibroblasts. Cytogenet Cell Genet. 1981;30(2):108–117. doi: 10.1159/000131597. [DOI] [PubMed] [Google Scholar]
  13. Salk D., Bryant E., Au K., Hoehn H., Martin G. M. Systematic growth studies, cocultivation, and cell hybridization studies of Werner syndrome cultured skin fibroblasts. Hum Genet. 1981;58(3):310–316. doi: 10.1007/BF00294930. [DOI] [PubMed] [Google Scholar]
  14. Salk D. Werner's syndrome: a review of recent research with an analysis of connective tissue metabolism, growth control of cultured cells, and chromosomal aberrations. Hum Genet. 1982;62(1):1–5. doi: 10.1007/BF00295598. [DOI] [PubMed] [Google Scholar]
  15. Scappaticci S., Cerimele D., Fraccaro M. Clonal structural chromosomal rearrangements in primary fibroblast cultures and in lymphocytes of patients with Werner's Syndrome. Hum Genet. 1982;62(1):16–24. doi: 10.1007/BF00295599. [DOI] [PubMed] [Google Scholar]
  16. Steel C. M., Woodward M. A., Davidson C., Philipson J., Arthur E. Non-random chromosome gains in human lymphoblastoid cell lines. Nature. 1977 Nov 24;270(5635):349–351. doi: 10.1038/270349a0. [DOI] [PubMed] [Google Scholar]
  17. Sutherland G. R. Fragile sites on human chromosomes: demonstration of their dependence on the type of tissue culture medium. Science. 1977 Jul 15;197(4300):265–266. doi: 10.1126/science.877551. [DOI] [PubMed] [Google Scholar]

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