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

Oncogene. 2001 Jul 27;20(33):4586-90. doi: 10.1038/sj.onc.1204617.


The INK4a/ARF locus encodes two unrelated cell cycle-regulatory proteins that both function in tumor suppression, p16INK4a and p14ARF. In human tumors including breast cancer, alterations affecting selectively p14ARF have been poorly analysed. We have performed a comprehensive analysis of the inactivation mechanisms (mutation, homozygous and hemizygous deletion, and promoter hypermethylation) in a large series of 100 primary breast carcinomas. RT-PCR showed expression variable of the p14ARF transcript, with 17% demonstrating overexpression and 26% demonstrating decreased expression. No detectable alterations were observed in the majority of cases with overexpressed p14ARF 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 and several poor prognostic parameters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Carcinoma / genetics*
  • Carcinoma / metabolism
  • Carcinoma / mortality
  • Cyclin-Dependent Kinase Inhibitor p16 / biosynthesis*
  • DNA Methylation
  • DNA, Complementary / genetics
  • Exons / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Gene Silencing*
  • Genes, p16*
  • Humans
  • Loss of Heterozygosity
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Polymorphism, Single-Stranded Conformational
  • Prognosis
  • Promoter Regions, Genetic
  • RNA, Messenger / biosynthesis
  • RNA, Neoplasm / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Deletion


  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Complementary
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm