Summary
The significance of the p53 tumour-suppressor gene in the oncogenesis of a variety of malignant tumours has been demonstrated over recent years. However, the role of p53 in human malignant melanoma is still unclear. Therefore, we investigated melanoma metastases from 11 patients cytogenetically and with fluorescence in situ hybridization (FISH) after short-term culture, employing a p53 region-specific probe for 17p13.1 and a probe detecting the centromere of chromosome 17. Furthermore, paraffin-embedded tissue samples from nine of these patients were investigated immunohistochemically for expression of the p53 protein. Deletions of the short arm of chromosome 17 were seen in six melanomas in cytogenetic analysis. With FISH, three malignant melanomas had clones with only one p53-allele and an additional four malignant melanomas showed a reduced number of signals at the p53 tumour-suppressor gene locus compared with signals for the centromeric region of chromosome 17. This was confirmed by immunohistochemistry. Our results suggest that the 17p11–13 region is frequently deleted in malignant melanomas and that p53 or other genes located on this band might contribute to the malignant potential of advanced melanoma.
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Akslen, L. A. & Morkve, O. (1992). Expression of p53 protein in cutaneous melanoma. Int J Cancer 52: 13–16.
Balch, C. M., Houghton, A. N., Milton, G. W., Sober, A. J. & Soong, S. J. (1992). Cutaneous Melanoma, JB Lippincott: Grand Rapids, New York
Cannan-Albright, L. A., Goldgar, D. E., Meyer, L. J., Lewis, C. M., Anderson, D. E., Fountain, J. W., Hegi, M. E., Wiseman, R. W., Petty, E. M., Bale, A. E., Olopade, O. I., Diaz, M. O., Kwiatkowsky, D. J., Piepkorn, M. W., Zone, J. J. & Skolnick, M. H. (1992). Assignment of a locus for familial melanoma, MLM, to chromosome 9p13–p22. Science 258: 1148–1152.
Carder, P., Wyllie, A. H., Purdie, C. A., Morris, R. G., White, S., Piris, J. & Bird, C. C. (1993). Stabilised p53 facilitates aneuploid clonal divergence in colorectal cancer. Oncogene 8: 1397–1401.
Catresana, J. S., Rubio, M-P & Vazquez, J. J. (1993). Lack of allelic deletion and point mutation as mechanism of p53 activation in human malignant melanoma. Int J Cancer 55: 562–565.
Chen, T. R. & Shaw, M. W. (1973). Stable chromosome changes in a human malignant melanoma. Cancer Res 33: 2042–2047.
Drach, J. (1994). Interphasenzytogenetik mittels Fluoreszenz-In-situ-Hybridisierung (FISH). Methoden der disgnostischen Hämatologie, Huber H, Löffler H, Faber V (eds). 119–124, Springer Verlag: Berlin
Drach, J., Angerler, J., Schuster, J., Rothermund, C., Thalhammer, R., Haas, O. A., Jäger, U., Fiegl, M., Geissler, K., Ludwig, K. & Huber, H. (1995). Interphase fluorescence in situ hydridization identifies chromosomal abnormalities in plasma cells from patients with monoclonal gammopathy of undetermined significance. Blood 86: 3915–3921.
Fountain, J. W., Karayiorgou, M., Ernstoff, M. S., Kirkwood, J. M., Vlock, D. R., Titus-Ernstoff, L., Bouchard, B., Vijayasaradhi, S., Houghton, A. N., Lahti, J., Kidd, V. J., Housman, D. E. & Dracopoli, N. C. (1992). Homozygous deletions within human chromosome band 9p21 in melanoma. Proc Natl Acad Sci USA 89: 10557–10561.
Frankel, R. H., Bayona, W., Koslow, M. & Newcomb, E. W. (1992). P53 mutations in human malignant gliomas: comparison of loss of heterozygosity with mutations frequency. Cancer Res 52: 1427–1433.
Gaidano, G., Serra, A., Guerrasio, A., Rege-Cambrin, G., Mazza, U. & Saglio, G. (1993). Genetic analysis of p53 and RB 1 tumour-suppressor-genes in blast crisis of chronic myeloid leukemia. Ann Haematol 68: 3–7.
Harris, C. C. (1993). p53: at the crossroads of molecular carcinogenesis and risk assessment. Science 262: 1980–1981.
Heim, S., Mandahl, N., Arheden, K., Giovanella, B. C., Yim, S. O., Stehlin, J. S. & Mitelman, F. (1988). Multiple karyotypic abnormalities, including structural rearrangements of 11p, in cell lines from malignant melanoma. Cancer Genet Cytogenet 35: 5–20.
Holland, E. A., Beaton, S. C., Edwards, B. G., Kefford, R. F. & Mann, G. J. (1994). Loss of heterozygosity and homozygous deletions on 9p21–22 in melanoma. Oncogene 9: 1361–1365.
Johnson, T. M., Smith, J. W., Nelson, B. R. & Chang, A. (1995). Continuing medical education: current therapy for cutaneous melanoma. J Am Acad Dermatol 32: 689–707.
Kamb, A., Gruis, N. A., Weaver-Feldhaus, J., Liu, Q., Harshman, K., Tavtigian, S. V., Stockert, E., Day, III R. S., Johnson, B. E. & Skolnick, M. H. (1994). A cell cycle regulator potentially involved in genesis of many tumour types. Science 264: 436–450.
Kanoko, M., Ueda, M., Nagano, T. & Ichihashi, M. (1995). Expression of p53 protein in melanoma progression. J Dermatol Sci 12: 97–103.
Koprowski, H., Herlyn, M., Balaban, G., Parmiter, A., Ross, A. & Nowell, P. (1985). Expression of the receptor for epidermal growth factor correlates with increased dosage of chromosome 7 in malignant melanoma. Somatic Cell Mol Genet 11: 297–302.
Kuerbitz, S. J., Plunkett, B. B., Walsh, W. V. & Kastan, M. B. (1992). Wild-type p53 is a cell cycle checkpoint determinant following irradiation. Proc Natl Acad Sci USA 89: 7491–7495.
Lee, H. M., Abrahamson, J. J. A. & Bernstein, A. (1994). DNA damage, oncogenesis and the p53 tumour-suppressor gene. Mutation Res 307: 573–581.
Levine, A. J. (1993). The tumour suppressor genes. Annu Rev Biochem 62: 623–651.
Lynch, H. T., Fusaro, R. M., Sandberg, A. A., Bixeman, H. A., Johnsen, L. R., Lynch, J. F., Ramesch, K. H. & Leppert, M. (1993). Chromosome instability and the FAMMM syndrome. Cancer Genet Cytogenet 71: 27–39.
Mitelman, F. (1995). An International System for Human Cytogenetic Nomenclature. Mitelman F (ed). S. Karger: Basle
Pederson, I. M., Bennet, J. W. & Wang, N. (1986). Nonrandom chromosome structural aberrations and oncogene loci in human malignant melanoma. Cancer Genet Cytogenet 20: 11–27.
Piepkorn, M. W. (1994). Genetic basis of susceptibility to melanoma. J Am Acad Dermatol 31: 1022–1039.
Pietenpol, J. A. & Vogelstein, B. (1993). No room at the p53 inn. Nature 365: 17–18.
Poremba, C., Yandell, D. W., Metze, D., Kamanabrou, D., Böcker, W. & Dockhorn-Dworniczak, B. (1995). Immunohistochemical detection of p53 in melanomas with rare p53 gene mutations is associated with mdm-2 overexpression. Oncol Res 7: 331–339.
Prives, C. & Manfredi, J. J. (1993). The p53 tumour suppressor protein: meeting review. Genes Dev 7: 529–534.
Saez-Santamaría, M. C., McNutt, N. S., Bogdany, J. K. & Shea, C. R. (1995). P53 expression is rare in cutaneous melanomas. Am J Dermatopathol 17: 344–349.
Saylors, R. L., Sidransky, D., Friedman, H. S., Bigner, S. H., Bigner, D. D., Vogelstein, B. & Brodeur, G. M. (1991). Infrequent p53 gene mutations in medulloblastomas. Cancer Res 51: 4721–4723.
Schweitzer, D. & Ambros, P. F. (1994). Chromosome banding: stain combinations for specific regions. Methods in Molecular Biology, Vol. 29: Chromosome Analysis Protocols, Gosden JR (ed). 97–112, Humana Press: Totowa, NJ
Skolnick, M. H., Cannon-Albright, L. A. & Kamb, A. (1994). Genetic predisposition to melanoma. Eur J Cancer 13: 1991–1995.
Stretch, J. R., Gatter, K. C., Ralfkiaer, E., Lane, D. P. & Harris, A. L. (1991). Expression of mutant p53 in melanoma. Cancer Res 51: 5976–5979.
Talve, L., Kainu, J., Collan, Y. & Ekfors, T. (1996). Immunohistochemical expression of p53 protein, mitotic index and nuclear morphometrie in primary malignant melanoma of the skin. Pathol Res Pract 192: 825–833.
Trent, J. M., Meyskens, F. L., Salmon, S. E., Ryschon, K., Leong, S. P., Davis, J. R. & McGee, D. L. (1990). Relation of cytogenetic abnormalities and clinical outcome in metastatic melanoma. N Engl J Med 322: 1508–1511.
Author information
Authors and Affiliations
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Okamoto, I., Pirc-Danoewinata, H., Ackermann, J. et al. Deletions of the region 17p11-13 in advanced melanoma revealed by cytogenetic analysis and fluorescence in situ hybridization. Br J Cancer 79, 131–137 (1999). https://doi.org/10.1038/sj.bjc.6690022
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bjc.6690022
Keywords
This article is cited by
-
Longitudinal Study of Recurrent Metastatic Melanoma Cell Lines Underscores the Individuality of Cancer Biology
Journal of Investigative Dermatology (2014)