Lack of mutation at p16INK4A gene but expression of aberrant p16INK4A RNA transcripts in human ovarian carcinoma

Alterations of the p16INK4A gene are frequent in various human cancers. We investigated p16INK4A gene status in 20 ovarian carcinomas by PCR (polymera se chain reaction), PCR-SSCP (polymerase chain reaction-single strand confo rmation polymorphism) and sequencing techniques. None of the primary tumors showed any mutational or deletional events. However, 19 out of 20 tumors d isplayed both a methylated and an unmethylated p16INK4A promoter. In some o f these samples, we detected aberrant p16INK4A transcripts, with partial de letions of both exons 1 and 2, which could not encode a functional p16INK4A protein. The sequences of the aberrant mRNA revealed common 4-7 nucleotide sequences before and after the deleted region, which might cause abnormal splicing of mRNA transcripts. These results suggest that both promoter meth ylation and aberrant mRNA processing may interfere with p16INK4A expression in ovarian rumors. (C) 2000 Elsevier Science Ireland Ltd. All rights reser ved.