SELECTIVE DELETION OF EXON 1-BETA OF THE P19(ARF) GENE IN METASTATIC MELANOMA CELL-LINES

The INK4A locus on 9p21 is deleted or rearranged in a large number of human cancers. The locus encodes two unrelated and independently actin g negative cell-cycle regulators, p16 and p19(ARF), arising in alterna te reading frames from a partly shared sequence. We analyzed five huma n melanoma cell lines for deletions at the INK4 loci and flanking micr osatellite markers on 9p21. All the cell lines displayed deletions of varying sizes. The metastatic cell line IGR-1 showed a large deletion between the markers D9S736 and D9S171. In the cell lines WM-115 and WM -266-4, the deletion included exon 1 alpha of p16, exon 1 beta of p19( ARF), and exon 2 of the INK4B (p15) gene. Two cell lines, SK-MEL-5 and A2058, had deletions confined to exon 1 beta and the microsatellite m arker D9S942. RT-PCR experiments showed the presence of the p16 and p1 5 transcripts and absence of p19(ARF) expression in both SK-MEL-5 and A2058 cell lines. The selective loss of the exon 1 beta of p19(ARF) an d retention of the p16 and p15 genes and their expressions in these tw o cell lines support the putative tumor suppressor role for the altern ate reading frame p19(ARF) gene. Genes Chromosomes Cancer 23:273-277, 1998. (C) 1998 Wiley-Liss, Inc.