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British Journal of Cancer (2000) 83, 1707–1714. doi:10.1054/bjoc.2000.1513
Published online 5 December 2000

Definition of the role of chromosome 9p21 in sporadic melanoma through genetic analysis of primary tumours and their metastases

G Palmieri1, A Cossu2, P A Ascierto3, G Botti3, M Strazzullo3, A Lissia2, M Colombino1, M Casula1, C Floris4, F Tanda2, M Pirastu1, G Castello3 and the Melanoma Cooperative Group5

  1. 1Institute of Molecular Genetics, C.N.R., Alghero (SS), Casella Postale, Santa Maria La Palma (Sassari), 07040, Italy
  2. 2Institute of Pathology, University of Sassari, Viale San Pietro 10, Sassari, 07100, Italy
  3. 3National Tumor Institute ‘G. Pascale', Via M. Semmola, Naples, 80131, Italy
  4. 4Oncologic Hospital ‘A: Businco’, A.S.L. 8, Via Jenner, Cagliari, 09100, Italy

5Melanoma Cooperative Group: Aprea P, Ascierto PA, Botti G, Caracò C, Castello G, Celentano E, Comella C, Daponte A, Graziano F, Mozzillo N, Parasole R, Picone A, National Tumor Institute, Naples, Italy; Bosco L, Prota G, Satriano R, University of Naples, Italy; D'Urso M, International Institute of Genetics and Biophysics, C.N.R., Naples, Italy; Palmieri G, Institute of Molecular Genetics, C.N.R., Alghero (SS), Italy

Received 16 May 2000; Revised 14 August 2000; Accepted 16 August 2000



Malignant melanoma (MM) is thought to arise by sequential accumulation of genetic alterations in normal melanocytes. Previous cytogenetic and molecular studies indicated the 9p21 as the chromosomal region involved in MM pathogenesis. In addition to the CDKN genes (p16/CDKN2A, p15/CDKN2B and p19ARF, frequently inactivated in familial MM), widely reported data suggested the presence within this region of other melanoma susceptibility gene(s). To clearly assess the role of the 9p21 region in sporadic melanoma, we evaluated the presence of microsatellite instability (MSI) and loss of heterozygosity (LOH) in primary tumours as well as in synchronous or asynchronous metastases obtained from the same MM patients, using 9 polymorphic markers from a 17-cM region at 9p21. LOH and MSI were found in 27 (41%) and 11 (17%), respectively, out of 66 primary tumours analysed. In corresponding 58 metastases, MSI was found at higher rate (22; 38%), whereas a quite identical pattern of allelic deletions with 27 (47%) LOH+ cases were observed. Although the CDKN locus was mostly affected by LOH, an additional region of common allelic deletion corresponding to marker D9S171 was also identified. No significant statistical correlation between any 9p21 genetic alteration (LOH, MSI or both) and clinicopathological parameters was observed. © 2000 Cancer Research Campaign


malignant melanoma; chromosome 9p21, polymerase chain reaction; microsatellite analysis; tumour progression



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