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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1992 Feb;83(2):159–164. doi: 10.1111/j.1349-7006.1992.tb00081.x

Length of Telomeric Repeats in Neuroblastoma: Correlation with Prognosis and Other Biological Characteristics

Eiso Hiyama 1,✉, Keiko Hiyama 3, Takashi Yokoyama 1, Toru Ichikawa 2, Yuichiro Matsuura 2
PMCID: PMC5918785  PMID: 1555997

Abstract

Telomeres are the physical ends of eukaryotic chromosomes. In view of reports of the reduction of telomeric repeats in human malignant tumors, we measured the lengths of telomeric repeats in 55 primary neuroblastomas. The average lengths of telomeric repeats in these tumors fell in a wide range (from 1.1 kb to more than 23 kb) relative to those in ganglioneuromas and normal peripheral mononuclear cells. The reduction of telomeric repeats was significantly correlated with advanced stages of tumor development, poor prognosis, and increased S‐phase fractions in tumor cells. On the other hand, three cases of Stage IV‐S tumors showed the reduction of telomeric repeats and low percentage of S‐phase fractions. These Stage IV‐S patients had a good prognosis with spontaneous regression of metastatic tumors.

Keywords: Key words, Neuroblastoma, Telomere, Prognosis, Progression

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REFERENCES

  • 1. ) Zakian , V. A.Structure and function of telomeres . Annu, Rev. Genet. , 23 , 579 – 604 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) Blackburn , E. H.Structure and function of telomeres . Nature , 350 , 569 – 573 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 3. ) Allshire , R. C. , Gosden , J. R. , Cross , S. H. , Cranston , G. , Rout , D. , Sugawara , N. , Szostak , J. W. , Fantes , P. A. and Hastie , N. D.Telomeric repeat from T. thermophila cross hybridizes with human telomeres . Nature , 332 , 656 – 659 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Allshire , R. C. , Dempster , M. and Hastie , N. D.Human telomeres contain at least three types of G‐rich repeat distributed non‐randomly . Nucleic Acids Res. , 17 , 4611 – 4627 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5. ) de Lange , T. , Shiue , L. , Myers , R. M. , Cox , D. R. , Naylor , S. L. , Killery , A. M. and Varmus , H. E.Stucture and variability of human chromosome ends . Mol. Cell Biol. , 10 , 518 – 527 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. ) Hastie , N. D. , Dempster , M. , Dunlop , M. G. , Thompson , A. M. , Green , D. K. and Allshire , R. C.Telomere reduction in human colorectal carcinoma and with ageing . Nature , 346 , 866 – 868 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 7. ) Harley , C. B. , Fucher , A. B. and Greider , C. W.Telomeres shorten during ageing of human fibroblasts . Nature , 345 , 458 – 460 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Shimada , H. , Chatten , J. , Newton , W. A. , Sachs , N. , Hamoudi , A. B. , Chiba , T. , Marsden , H. B. and Misugi , K.Histopathologic prognostic factors in neuroblastic tumors: definition of subtypes of ganglioneuroblastoma and an age‐linked classification of neuroblastomas . J. Natl. Cancer Inst. , 73 , 405 – 416 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 9. ) Gansler , T. , Chatten , J. , Varello , M. , Bunin , G. R. and Atkinson , B.Flow cytometric DNA analysis of neuroblastoma: correlation with histology and clinical outcome . Cancer , 58 , 2453 – 2458 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 10. ) Taylor , S. R. , Blatt , J. , Costantino , J. P. , Roederer , M. and Murphy , R. F.Flow cytometric DNA analysis of neuroblastoma and ganglioneuroma: a 10‐year retrospective study . Cancer , 62 , 749 – 754 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Bourhis , J. , DeVathaire , F. , Wilson , G. D. , Hartmann , M. J. , Terrier‐Lacombe , M. J. , Boccon‐Gibod , L. , McNally , N. J. , Lemerle , J. , Riou , G. and Benard , J.Combined analysis of DNA ploidy index and N‐myc genomic content in neuroblastoma . Cancer Res. , 51 , 33 – 36 ( 1991. ). [PubMed] [Google Scholar]
  • 12. ) Brodeur , G. M. , Seeger , R. C. , Schwab , M. , Varmus , H. E. and Bishop , J. M.Amplification of N‐myc in untreated human neuroblastomas correlates with advanced disease stage . Science , 224 , 1121 – 1124 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 13. ) Seeger , R. C. , Brodeur , G. M. , Sather , H. , Dalton , A. , Siegel , S. E. , Wong , K. Y. and Hammond , D.Association of multiple copies of the N‐myc oncogene with rapid progression of neuroblastomas . N. Engl. J. Med. , 313 , 1111 – 1116 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 14. ) Evans , A. E. , D'Angio , G. J. and Randolph , J.A proposed staging for children with neuroblastoma . Cancer , 27 , 374 – 378 ( 1971. ). [DOI] [PubMed] [Google Scholar]
  • 15. ) Hiyama , E. , Yokoyama , T. , Ichikawa , T. , Ishii , T. and Hiyama , K.N‐myc gene amplification and other prognosis‐associated factors in neuroblastoma . J. Pediatr. Surg , 25 , 1095 – 1099 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 16. ) Moyzis , R. K. , Buckingham , J. M. , Cram , L. S. , Dani , M. , Deaven , L. L. , Jones , M. D. , Meyne , J. , Ratliff , R. L. and Wu , J. R.A highly conserved repetitive DNA sequences, (TTAGGG)n, present at the telomeres of human chromosomes . Proc. Natl Acad. Sci. USA , 85 , 6622 – 6626 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. ) Vindeløv , L. L. , Christensen , I. J. and Nissen , N. I.A detergent‐trypsin method for the preparation of nuclei for flow cytometric DNA analysis . Cytometry , 3 , 323 – 327 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 18. ) Milthorpe , B.FMFPAKI: a program package for routine analysis of single parameter flow microfluorimetric data on a low cost mini‐computer . Comput. Biomed. Res. , 13 , 417 – 429 ( 1980. ). [DOI] [PubMed] [Google Scholar]
  • 19. ) Peto , R. , Pike , M. C. , Armitage , P. , Breslow , N. E. , Cox , D. R. , Howard , S. V. , Mantel , N. , McPherson , K. , Peto , J. and Smith , P. G.Design and analysis of randomized clinical trials requiring prolonged observation of each patient . Br. J. Cancer , 35 , 1 – 39 ( 1977. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20. ) Hiyama , E. , Hiyama , K. , Yokoyama , T. and Ishii , T.Immunohistochemical analysis of N‐myc protein expression in neuroblastoma: correlation with prognosis of patients . J. Pediatr. Surg. , 26 , 838 – 843 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Evans , A. E. , Baum , E. and Chard , R.Do infants with stage IV‐S neuroblastoma need treatment ? Arch. Dis. Child , 56 , 271 – 274 ( 1981. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22. ) Haas , D. , Ablin , A. R. , Miller , C. , Zoger , S. and Matthay , K. K.Complete pathologic maturation and regression of stage IVS neuroblastoma without treatment . Cancer , 62 , 818 – 825 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 23. ) Evans , A. E. , Gerson , J. and Schnaufer , L.Spontaneous regression of neuroblastoma . Natl. Cancer Inst. Monogr. , 44 , 49 – 54 ( 1976. ). [PubMed] [Google Scholar]
  • 24. ) Morin , G. B.The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats . Cell , 59 , 521 – 529 ( 1989. ). [DOI] [PubMed] [Google Scholar]

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