Characterization of 9p21 copy number alterations in human melanoma by fluorescence in situ hybridization

Alteration of the CDKN2A (alias p16) tumor suppressor gene, located on 9p21, occurs frequently in familial and sporadic melanomas. Beside CDKN2A, other genes (e.g., CDKN2B, and ARF/p14ARF, long considered distinct from CDKN2A) on this locus are often deleted or mutated in a large number of tumors including glioma, bladder cancer, and lung cancer. The aim of this study was to evaluate the deletion pattern of the 9p21 locus on a cell-by-cell basis in a large number of melanoma samples using fluorescence in situ hybridization (FISH). In an analysis of 81 primary lesions targeting the 9p21 region and chromosome 9 centromere, high frequency of 9p21 loss (84%) was found. Deletion of 9p21 was present in both early- and late-stage melanomas with similar frequencies. Extra 9p21 copies were rarely seen; they were always associated with polysomy 9 and were observed only in advanced stage melanomas (6 tumors). This FISH study strengthens the hypothesis that the loss of 9p21 occurs frequently in primary melanoma, that the deletion is present in early and late stages of the disease with similar frequency, and that it affects a large extent of the locus.