Selective deletion of exon 1β of the p19ARF gene in metastatic melanoma cell lines

✍ Scribed by Rajiv Kumar; Ilari Sauroja; Kari Punnonen; Christer Jansen; Kari Hemminki

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 195 KB
• Volume: 23
• Category: Article
• ISSN: 1045-2257
• DOI: 10.1002/(sici)1098-2264(199811)23:3<273::aid-gcc11>3.0.co;2-n

✦ Synopsis

The INK4A locus on 9p21 is deleted or rearranged in a large number of human cancers. The locus encodes two unrelated and independently acting negative cell-cycle regulators, p16 and p19 ARF , arising in alternate reading frames from a partly shared sequence. We analyzed five human melanoma cell lines for deletions at the INK4 loci and flanking microsatellite 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␣ of p16, exon 1␤ 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␤ and the microsatellite marker D9S942. RT-PCR experiments showed the presence of the p16 and p15 transcripts and absence of p19 ARF expression in both SK-MEL-5 and A2058 cell lines. The selective loss of the exon 1␤ of p19 ARF and retention of the p16 and p15 genes and their expressions in these two cell lines support the putative tumor suppressor role for the alternate reading frame p19 ARF gene.