Selective deletion of p14(ARF) exon 1β of the INK4a locus in oral squamous cell carcinomas of Indians

Abstract 

The tumor suppressor gene — p16 INK4/CDKN2/MTS1 and its alternate splice product p14 (ARF), constitute the INK4a locus. We have examined the integrity of exon 1β of p14(ARF) gene of oral squamous cell carcinomas (n=58) in untreated Indian patients. No mutations were detected in this region by PCR-SSCP analysis of the tumor DNA’s. Further, PCR-based analysis revealed homozygous deletions of exon 1β in 14 of the 58 tumors; these results were confirmed by hybridization of tumor DNAs with exon 1β specific probe. The deletions were limited to the exon 1β while the exons coding p16/INK4 were not affected. Except in two cases these deletions were mutually exclusive to the p53 inactivating mutations. These observations suggest an alternate mechanism of loss of p14(ARF) in the genesis of oral squamous cell carcinomas.

Keywords:  INK4 locus, p14(ARF), Exon 1β, Oral cancers, Selective deletion