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

Malignant melanoma (MM) is thought to arise by sequential accumulation of g enetic alterations in normal melanocytes. Previous cytogenetic and molecula r studies indicated the 9p21 as the chromosomal region involved in MM patho genesis. In addition to the CDKN genes (p16/CDKN2A, p15/CDKN2B and p19(ARF) , frequently inactivated in familial MM): widely reported data suggested th e presence within this region of other melanoma susceptibility gene(s). To clearly assess the role of the 9p21 region in sporadic melanoma, we evaluat ed the presence of microsatellite instability (MSI) and loss of heterozygos ity (LOH) in primary tumours as well as in synchronous or asynchronous meta stases 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%), r espectively, out of 66 primary tumours analysed. In corresponding 58 metast ases, MSI was found at higher rate (22; 38%), whereas a quite identical pat tern of allelic deletions with 27 (47%) LOH+ cases were observed. Although the CDKN locus was mostly affected by LOH, an additional region of common a llelic deletion corresponding to marker D9S171 was also identified. No sign ificant statistical correlation between any 9p21 genetic alteration (LOH. M SI or both) and clinicopathological parameters was observed. (C) 2000 Cance r Research Campaign.