Abstract B82: High frequency of hypermethylation at the 14-3-3 sigma to gene silencing in breast cancer.

Abstract

Background: Expression of 14-3-3 sigma is induced in response to DNA damage, and causes cells to arrest in G(2). Hypermethylation of CpG islands located in the promoter regions of tumor suppressor genes is now firmly established as an important mechanism for gene inactivation. Objetive: To study the relation of 14-3-3 sigma gene promoter hypermethylation and its transcription expression levels in sporadic breast carcinogenesis. Material and Methods:This is a prospective study we quantified methylation levels of promoter 14-3-3 gene in 107 women with breast cancer and 108 control subjects by Real Time QMS-PCR SYBR green and analyzed association with prognostics factor in breast cancer. Results: Median age was 58 years (32-88); 69% were postmenopausal women. Nodal involvement N0; 63%, N1;30%, N2;7%), tumor size (T1;58%, T2;35%, T3;4%, T4;4%) and grade G1; 20%, G2;37%, G3;30%). The methylation of 14-3-3σ were 60% of sporadic breast cancer patients and were 34% of normal breast (p=0.0047). The methylation of 14-3-3σ gene in serum was markedly related with T3-4 stage (p<0.05), nodal positive status (p<0.05) and poor outcome. With a median follow up 6 years we saw more probability of developing distance metastasis in patients with methylation 14-3-3σ (p>0.05). Conclusions: The recent identification of novel 14-3-3sigma-associated proteins by a targeted proteomics approach implies that 14-3-3sigma regulates diverse cellular processes, which may become deregulated after silencing of 14-3-3sigma expression in cancer cells. Therefore, it is possible that loss of σ expression contributes to malignant transformation by impairing the G2 cell cycle checkpoint function, thus allowing an accumulation of genetic defects. Perhaps in the detection of CpG methylation of 14-3-3σ may be used for diagnostic and prognostic purposes Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B82.