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British Journal of Cancer logoLink to British Journal of Cancer
. 2000 Jan 18;82(2):330–338. doi: 10.1054/bjoc.1999.0923

Association of specific chromosome alterations with tumour phenotype in posterior uveal melanoma

K Sisley 1,2, M A Parsons 2, J Garnham 3, A M Potter 3, D Curtis 3, R C Rees 4, I G Rennie 2
PMCID: PMC2363277  PMID: 10646885

Abstract

Posterior uveal melanomas have recurrent alterations of chromosomes 1, 3, 6 and 8. In particular, changes of chromosomes 3 and 8 occur in association, appear to characterize those tumours with a ciliary body component, and have been shown to be of prognostic significance. The relevance of other chromosome alterations is less certain. We have performed cytogenetic analysis on 42 previously untreated primary posterior uveal melanomas. Of interest was the observation that as tumour size increased the involvement of specific chromosome changes, and the amount of chromosome abnormalities likewise increased. Loss, or partial deletions, of the short arm of chromosome 1 were found to associate with larger ciliary body melanomas; typically, loss of the short arm resulted from unbalanced translocations, the partners of which varied. Trisomy of chromosome 21 occurred more often in ciliary body melanomas, whilst rearrangements of chromosomes 6 and 11 were primarily related to choroidal melanomas. Our results imply that alterations of chromosome 1 are important in the progression of some uveal melanomas, and that other chromosome abnormalities, besides those of chromosomes 3 and 8, are associated with ocular tumours of particular locations. © 2000 Cancer Research Campaign

Keywords: cytogenetics, translocation, uveal melanoma, phenotype

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Selected References

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  1. Agapova L. S., Ilyinskaya G. V., Turovets N. A., Ivanov A. V., Chumakov P. M., Kopnin B. P. Chromosome changes caused by alterations of p53 expression. Mutat Res. 1996 Jul 5;354(1):129–138. doi: 10.1016/0027-5107(96)00062-0. [DOI] [PubMed] [Google Scholar]
  2. Cahill D. P., Lengauer C., Yu J., Riggins G. J., Willson J. K., Markowitz S. D., Kinzler K. W., Vogelstein B. Mutations of mitotic checkpoint genes in human cancers. Nature. 1998 Mar 19;392(6673):300–303. doi: 10.1038/32688. [DOI] [PubMed] [Google Scholar]
  3. Canning C. R., Hungerford J. Familial uveal melanoma. Br J Ophthalmol. 1988 Apr;72(4):241–243. doi: 10.1136/bjo.72.4.241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dahlenfors R., Törnqvist G., Wettrell K., Mark J. Cytogenetical observations in nine ocular malignant melanomas. Anticancer Res. 1993 Sep-Oct;13(5A):1415–1420. [PubMed] [Google Scholar]
  5. Dracopoli N. C., Harnett P., Bale S. J., Stanger B. Z., Tucker M. A., Housman D. E., Kefford R. F. Loss of alleles from the distal short arm of chromosome 1 occurs late in melanoma tumor progression. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4614–4618. doi: 10.1073/pnas.86.12.4614. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Egan K. M., Seddon J. M., Glynn R. J., Gragoudas E. S., Albert D. M. Epidemiologic aspects of uveal melanoma. Surv Ophthalmol. 1988 Jan-Feb;32(4):239–251. doi: 10.1016/0039-6257(88)90173-7. [DOI] [PubMed] [Google Scholar]
  7. Gordon K. B., Thompson C. T., Char D. H., O'Brien J. M., Kroll S., Ghazvini S., Gray J. W. Comparative genomic hybridization in the detection of DNA copy number abnormalities in uveal melanoma. Cancer Res. 1994 Sep 1;54(17):4764–4768. [PubMed] [Google Scholar]
  8. Healy E., Rehman I., Angus B., Rees J. L. Loss of heterozygosity in sporadic primary cutaneous melanoma. Genes Chromosomes Cancer. 1995 Feb;12(2):152–156. doi: 10.1002/gcc.2870120211. [DOI] [PubMed] [Google Scholar]
  9. Horsman D. E., White V. A. Cytogenetic analysis of uveal melanoma. Consistent occurrence of monosomy 3 and trisomy 8q. Cancer. 1993 Feb 1;71(3):811–819. doi: 10.1002/1097-0142(19930201)71:3<811::aid-cncr2820710325>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
  10. Johansson B., Mertens F., Mitelman F. Primary vs. secondary neoplasia-associated chromosomal abnormalities--balanced rearrangements vs. genomic imbalances? Genes Chromosomes Cancer. 1996 Jul;16(3):155–163. doi: 10.1002/(SICI)1098-2264(199607)16:3<155::AID-GCC1>3.0.CO;2-Y. [DOI] [PubMed] [Google Scholar]
  11. Kokalj-Vokac N., Alemeida A., Gerbault-Seureau M., Malfoy B., Dutrillaux B. Two-color FISH characterization of i(1q) and der(1;16) in human breast cancer cells. Genes Chromosomes Cancer. 1993 May;7(1):8–14. doi: 10.1002/gcc.2870070103. [DOI] [PubMed] [Google Scholar]
  12. Magauran R. G., Gray B., Small K. W. Chromosome 9 abnormality in choroidal melanoma. Am J Ophthalmol. 1994 Jan 15;117(1):109–111. doi: 10.1016/s0002-9394(14)73025-9. [DOI] [PubMed] [Google Scholar]
  13. McLean M. J., Foster W. D., Zimmerman L. E. Prognostic factors in small malignant melanomas of choroid and ciliary body. Arch Ophthalmol. 1977 Jan;95(1):48–58. doi: 10.1001/archopht.1977.04450010050004. [DOI] [PubMed] [Google Scholar]
  14. Ohta M., Berd D., Shimizu M., Nagai H., Cotticelli M-G, Mastrangelo M., Shields J. A., Shields C. L., Croce C. M., Huebner K. Deletion mapping of chromosome region 9p21-p22 surrounding the CDKN2 locus in melanoma. Int J Cancer. 1996 Mar 15;65(6):762–767. doi: 10.1002/(SICI)1097-0215(19960315)65:6<762::AID-IJC9>3.0.CO;2-X. [DOI] [PubMed] [Google Scholar]
  15. Prescher G., Bornfeld N., Becher R. Nonrandom chromosomal abnormalities in primary uveal melanoma. J Natl Cancer Inst. 1990 Nov 21;82(22):1765–1769. doi: 10.1093/jnci/82.22.1765. [DOI] [PubMed] [Google Scholar]
  16. Prescher G., Bornfeld N., Becher R. Two subclones in a case of uveal melanoma. Relevance of monosomy 3 and multiplication of chromosome 8q. Cancer Genet Cytogenet. 1994 Oct 15;77(2):144–146. doi: 10.1016/0165-4608(94)90230-5. [DOI] [PubMed] [Google Scholar]
  17. Prescher G., Bornfeld N., Friedrichs W., Seeber S., Becher R. Cytogenetics of twelve cases of uveal melanoma and patterns of nonrandom anomalies and isochromosome formation. Cancer Genet Cytogenet. 1995 Mar;80(1):40–46. doi: 10.1016/0165-4608(94)00165-8. [DOI] [PubMed] [Google Scholar]
  18. Prescher G., Bornfeld N., Hirche H., Horsthemke B., Jöckel K. H., Becher R. Prognostic implications of monosomy 3 in uveal melanoma. Lancet. 1996 May 4;347(9010):1222–1225. doi: 10.1016/s0140-6736(96)90736-9. [DOI] [PubMed] [Google Scholar]
  19. Prescher G., Bornfeld N., Horsthemke B., Becher R. Chromosomal aberrations defining uveal melanoma of poor prognosis. Lancet. 1992 Mar 14;339(8794):691–692. [PubMed] [Google Scholar]
  20. Ray M. E., Su Y. A., Meltzer P. S., Trent J. M. Isolation and characterization of genes associated with chromosome-6 mediated tumor suppression in human malignant melanoma. Oncogene. 1996 Jun 20;12(12):2527–2533. [PubMed] [Google Scholar]
  21. Rennie I. G. Diagnosis and treatment of ocular melanomas. Br J Hosp Med. 1991 Sep;46(3):144–156. [PubMed] [Google Scholar]
  22. Scotto J., Fraumeni J. F., Jr, Lee J. A. Melanomas of the eye and other noncutaneous sites: epidemiologic aspects. J Natl Cancer Inst. 1976 Mar;56(3):489–491. doi: 10.1093/jnci/56.3.489. [DOI] [PubMed] [Google Scholar]
  23. Singh A. D., Boghosian-Sell L., Wary K. K., Shields C. L., De Potter P., Donoso L. A., Shields J. A., Cannizzaro L. A. Cytogenetic findings in primary uveal melanoma. Cancer Genet Cytogenet. 1994 Feb;72(2):109–115. doi: 10.1016/0165-4608(94)90125-2. [DOI] [PubMed] [Google Scholar]
  24. Singh A. D., Shields C. L., De Potter P., Shields J. A., Trock B., Cater J., Pastore D. Familial uveal melanoma. Clinical observations on 56 patients. Arch Ophthalmol. 1996 Apr;114(4):392–399. doi: 10.1001/archopht.1996.01100130388005. [DOI] [PubMed] [Google Scholar]
  25. Sisley K., Brand C., Parsons M. A., Maltby E., Rees R. C., Rennie I. G. Cytogenetics of iris melanomas: disparity with other uveal tract melanomas. Cancer Genet Cytogenet. 1998 Mar;101(2):128–133. doi: 10.1016/s0165-4608(97)00230-6. [DOI] [PubMed] [Google Scholar]
  26. Sisley K., Cottam D. W., Rennie I. G., Parsons M. A., Potter A. M., Potter C. W., Rees R. C. Non-random abnormalities of chromosomes 3, 6, and 8 associated with posterior uveal melanoma. Genes Chromosomes Cancer. 1992 Oct;5(3):197–200. doi: 10.1002/gcc.2870050304. [DOI] [PubMed] [Google Scholar]
  27. Sisley K., Rennie I. G., Cottam D. W., Potter A. M., Potter C. W., Rees R. C. Cytogenetic findings in six posterior uveal melanomas: involvement of chromosomes 3, 6, and 8. Genes Chromosomes Cancer. 1990 Sep;2(3):205–209. doi: 10.1002/gcc.2870020307. [DOI] [PubMed] [Google Scholar]
  28. Sisley K., Rennie I. G., Parsons M. A., Jacques R., Hammond D. W., Bell S. M., Potter A. M., Rees R. C. Abnormalities of chromosomes 3 and 8 in posterior uveal melanoma correlate with prognosis. Genes Chromosomes Cancer. 1997 May;19(1):22–28. doi: 10.1002/(sici)1098-2264(199705)19:1<22::aid-gcc4>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
  29. Speicher M. R., Prescher G., du Manoir S., Jauch A., Horsthemke B., Bornfeld N., Becher R., Cremer T. Chromosomal gains and losses in uveal melanomas detected by comparative genomic hybridization. Cancer Res. 1994 Jul 15;54(14):3817–3823. [PubMed] [Google Scholar]
  30. Sunba M. S., Rahi A. H., Morgan G. Tumors of the anterior uvea. I. Metastasizing malignant melanoma of the iris. Arch Ophthalmol. 1980 Jan;98(1):82–85. doi: 10.1001/archopht.1980.01020030084004. [DOI] [PubMed] [Google Scholar]
  31. Surrallés J., Darroudi F., Natarajan A. T. Low level of DNA repair in human chromosome 1 heterochromatin. Genes Chromosomes Cancer. 1997 Oct;20(2):173–184. [PubMed] [Google Scholar]
  32. Tappin M. J., Parsons M. A., Sisley K., Rees R. C., Rennie I. G. Two cases of double melanoma of the uvea. Eye (Lond) 1996;10(Pt 5):600–602. doi: 10.1038/eye.1996.137. [DOI] [PubMed] [Google Scholar]
  33. White V. A., Chambers J. D., Courtright P. D., Chang W. Y., Horsman D. E. Correlation of cytogenetic abnormalities with the outcome of patients with uveal melanoma. Cancer. 1998 Jul 15;83(2):354–359. [PubMed] [Google Scholar]
  34. White V. A., Horsman D. E., Rootman J. Cytogenetic characterization of an iris melanoma. Cancer Genet Cytogenet. 1995 Jul 1;82(1):85–87. doi: 10.1016/0165-4608(94)00217-y. [DOI] [PubMed] [Google Scholar]
  35. Wiltshire R. N., Elner V. M., Dennis T., Vine A. K., Trent J. M. Cytogenetic analysis of posterior uveal melanoma. Cancer Genet Cytogenet. 1993 Mar;66(1):47–53. doi: 10.1016/0165-4608(93)90148-f. [DOI] [PubMed] [Google Scholar]
  36. Wooster R., Bignell G., Lancaster J., Swift S., Seal S., Mangion J., Collins N., Gregory S., Gumbs C., Micklem G. Identification of the breast cancer susceptibility gene BRCA2. Nature. 1995 Dec 21;378(6559):789–792. doi: 10.1038/378789a0. [DOI] [PubMed] [Google Scholar]

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