Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1996 Nov;74(10):1620–1626. doi: 10.1038/bjc.1996.598

An increased NM23H1 copy number may be a poor prognostic factor independent of LOH on 1p in neuroblastomas.

O Takeda 1, M Handa 1, T Uehara 1, N Maseki 1, A Sakashita 1, M Sakurai 1, N Kanda 1, Y Arai 1, Y Kaneko 1
PMCID: PMC2074847  PMID: 8932344

Abstract

In a study of 154 neuroblastomas, loss of heterozygosity (LOH) was observed on 1p (13%, 19/143), 11q (19%, 11/59), 14q (15%, 15/97), 17p (5%, 5/105) and 17q (17%, 9/52). We also found an increase in NM23H1 copy number in 14% (13/95) of neuroblastomas. All except one tumour with an increased copy number stained positive with anti-NM23H1 monoclonal antibody. Event-free survival (EFS) was significantly shorter in 19 patients with LOH on 1p than in 128 without (41% vs 77% 4 year EFS, P=0.0093), and in 13 patients with increased NM23H1 copy numbers than in 82 with normal copy numbers of the gene (61% vs 84% 4 year EFS, P=0.0103). LOH on 11q, 14q or 17q did not affect EFS. Most tumours with LOH on 1p, increased NM23H1 copy numbers or MYCN amplification occurred in patients aged 12 months or more, those with advanced stage disease, and those who showed near diploidy or pseudodiploidy. However, LOH on 1p was found in only 1 of the 13 tumours with increased NM23H1 copy numbers, and MYCN amplification of four copies occurred in only one other such tumour. These findings suggest that the increased NM23H1 copy number may be a predictor for poor prognosis, independent of LOH on 1p, and probably also of MYCN amplification.

Full text

PDF
1620

Images in this article

1621Figure 1
on p.1621
1623Figure 4
on p.1623

Selected References

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

  1. Bevilacqua G., Sobel M. E., Liotta L. A., Steeg P. S. Association of low nm23 RNA levels in human primary infiltrating ductal breast carcinomas with lymph node involvement and other histopathological indicators of high metastatic potential. Cancer Res. 1989 Sep 15;49(18):5185–5190. [PubMed] [Google Scholar]
  2. Caron H. Allelic loss of chromosome 1 and additional chromosome 17 material are both unfavourable prognostic markers in neuroblastoma. Med Pediatr Oncol. 1995 Apr;24(4):215–221. doi: 10.1002/mpo.2950240402. [DOI] [PubMed] [Google Scholar]
  3. Chang C. L., Zhu X. X., Thoraval D. H., Ungar D., Rawwas J., Hora N., Strahler J. R., Hanash S. M., Radany E. Nm23-H1 mutation in neuroblastoma. Nature. 1994 Aug 4;370(6488):335–336. doi: 10.1038/370335a0. [DOI] [PubMed] [Google Scholar]
  4. Evans A. E., D'Angio G. J., Randolph J. A proposed staging for children with neuroblastoma. Children's cancer study group A. Cancer. 1971 Feb;27(2):374–378. doi: 10.1002/1097-0142(197102)27:2<374::aid-cncr2820270221>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
  5. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  6. Fong C. T., Dracopoli N. C., White P. S., Merrill P. T., Griffith R. C., Housman D. E., Brodeur G. M. Loss of heterozygosity for the short arm of chromosome 1 in human neuroblastomas: correlation with N-myc amplification. Proc Natl Acad Sci U S A. 1989 May;86(10):3753–3757. doi: 10.1073/pnas.86.10.3753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fong C. T., White P. S., Peterson K., Sapienza C., Cavenee W. K., Kern S. E., Vogelstein B., Cantor A. B., Look A. T., Brodeur G. M. Loss of heterozygosity for chromosomes 1 or 14 defines subsets of advanced neuroblastomas. Cancer Res. 1992 Apr 1;52(7):1780–1785. [PubMed] [Google Scholar]
  8. GEHAN E. A. A GENERALIZED WILCOXON TEST FOR COMPARING ARBITRARILY SINGLY-CENSORED SAMPLES. Biometrika. 1965 Jun;52:203–223. [PubMed] [Google Scholar]
  9. Gilles A. M., Presecan E., Vonica A., Lascu I. Nucleoside diphosphate kinase from human erythrocytes. Structural characterization of the two polypeptide chains responsible for heterogeneity of the hexameric enzyme. J Biol Chem. 1991 May 15;266(14):8784–8789. [PubMed] [Google Scholar]
  10. Hailat N., Keim D. R., Melhem R. F., Zhu X. X., Eckerskorn C., Brodeur G. M., Reynolds C. P., Seeger R. C., Lottspeich F., Strahler J. R. High levels of p19/nm23 protein in neuroblastoma are associated with advanced stage disease and with N-myc gene amplification. J Clin Invest. 1991 Jul;88(1):341–345. doi: 10.1172/JCI115299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Leone A., Seeger R. C., Hong C. M., Hu Y. Y., Arboleda M. J., Brodeur G. M., Stram D., Slamon D. J., Steeg P. S. Evidence for nm23 RNA overexpression, DNA amplification and mutation in aggressive childhood neuroblastomas. Oncogene. 1993 Apr;8(4):855–865. [PubMed] [Google Scholar]
  12. Murakami Y., Hayashi K., Sekiya T. Detection of aberrations of the p53 alleles and the gene transcript in human tumor cell lines by single-strand conformation polymorphism analysis. Cancer Res. 1991 Jul 1;51(13):3356–3361. [PubMed] [Google Scholar]
  13. Nakamura Y., Lathrop M., O'Connell P., Leppert M., Kamboh M. I., Lalouel J. M., White R. Frequent recombination is observed in the distal end of the long arm of chromosome 14. Genomics. 1989 Jan;4(1):76–81. doi: 10.1016/0888-7543(89)90317-0. [DOI] [PubMed] [Google Scholar]
  14. Okada K., Urano T., Goi T., Baba H., Yamaguchi A., Furukawa K., Shiku H. Isolation of human nm23 genomes and analysis of loss of heterozygosity in primary colorectal carcinomas using a specific genomic probe. Cancer Res. 1994 Aug 1;54(15):3979–3982. [PubMed] [Google Scholar]
  15. Sawada T., Hirayama M., Nakata T., Takeda T., Takasugi N., Mori T., Maeda K., Koide R., Hanawa Y., Tsunoda A. Mass screening for neuroblastoma in infants in Japan. Interim report of a mass screening study group. Lancet. 1984 Aug 4;2(8397):271–273. doi: 10.1016/s0140-6736(84)90311-8. [DOI] [PubMed] [Google Scholar]
  16. Schleiermacher G., Peter M., Michon J., Hugot J. P., Vielh P., Zucker J. M., Magdelénat H., Thomas G., Delattre O. Two distinct deleted regions on the short arm of chromosome 1 in neuroblastoma. Genes Chromosomes Cancer. 1994 Aug;10(4):275–281. doi: 10.1002/gcc.2870100409. [DOI] [PubMed] [Google Scholar]
  17. Srivatsan E. S., Ying K. L., Seeger R. C. Deletion of chromosome 11 and of 14q sequences in neuroblastoma. Genes Chromosomes Cancer. 1993 May;7(1):32–37. doi: 10.1002/gcc.2870070106. [DOI] [PubMed] [Google Scholar]
  18. Steeg P. S., Bevilacqua G., Kopper L., Thorgeirsson U. P., Talmadge J. E., Liotta L. A., Sobel M. E. Evidence for a novel gene associated with low tumor metastatic potential. J Natl Cancer Inst. 1988 Apr 6;80(3):200–204. doi: 10.1093/jnci/80.3.200. [DOI] [PubMed] [Google Scholar]
  19. Suzuki T., Yokota J., Mugishima H., Okabe I., Ookuni M., Sugimura T., Terada M. Frequent loss of heterozygosity on chromosome 14q in neuroblastoma. Cancer Res. 1989 Mar 1;49(5):1095–1098. [PubMed] [Google Scholar]
  20. Takayama H., Suzuki T., Mugishima H., Fujisawa T., Ookuni M., Schwab M., Gehring M., Nakamura Y., Sugimura T., Terada M. Deletion mapping of chromosomes 14q and 1p in human neuroblastoma. Oncogene. 1992 Jun;7(6):1185–1189. [PubMed] [Google Scholar]
  21. Takeda O., Homma C., Maseki N., Sakurai M., Kanda N., Schwab M., Nakamura Y., Kaneko Y. There may be two tumor suppressor genes on chromosome arm 1p closely associated with biologically distinct subtypes of neuroblastoma. Genes Chromosomes Cancer. 1994 May;10(1):30–39. doi: 10.1002/gcc.2870100106. [DOI] [PubMed] [Google Scholar]
  22. Urano T., Furukawa K., Shiku H. Expression of nm23/NDP kinase proteins on the cell surface. Oncogene. 1993 May;8(5):1371–1376. [PubMed] [Google Scholar]
  23. Varesco L., Caligo M. A., Simi P., Black D. M., Nardini V., Casarino L., Rocchi M., Ferrara G., Solomon E., Bevilacqua G. The NM23 gene maps to human chromosome band 17q22 and shows a restriction fragment length polymorphism with BglII. Genes Chromosomes Cancer. 1992 Jan;4(1):84–88. doi: 10.1002/gcc.2870040113. [DOI] [PubMed] [Google Scholar]
  24. Weith A., Martinsson T., Cziepluch C., Brüderlein S., Amler L. C., Berthold F., Schwab M. Neuroblastoma consensus deletion maps to 1p36.1-2. Genes Chromosomes Cancer. 1989 Nov;1(2):159–166. doi: 10.1002/gcc.2870010209. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES