Analysis of genetic and epigenetic processes that influence p14ARF expression in breast cancer

The INK4a/ARF locus encodes two unrelated cell cycle-regulatory proteins th at both function in tumor suppression, p16INK4a and p14ARF. In human tumors including breast cancer, alterations affecting selectively p14ARF have bee n poorly analysed. We have performed a comprehensive analysis of the inacti vation mechanisms (mutation, homozygous and hemizygous deletion, and promot er hypermethylation) in a large series of 100 primary breast carcinomas. RT -PCR showed expression variable of the p14ARF transcript, with 17% demonstr ating overexpression and 26% demonstrating decreased expression. No detecta ble alterations were observed in the majority of cases with overexpressed p 14ARF mRNA, but 77% of tumors with decreased expression presented at least one of these genetic/ epigenetic alterations. Nevertheless, a statistically significant correlation was observed between decreased p14ARF expression a nd several poor prognostic parameters.