Abstract

Abstract Our recent studies have shown that human SET1, a key element of highly conserved multi-protein histone methyl transferase (HMT) complex known to catalyze methylation of histone H3 lysine 4 (H3K4) and regulating expression of specific genes important for the malignant phenotype, differentially over-expressed in the cancer cells. RT-PCR competition assay were developed using oligonucleotides, designed from the conserved sequences from the flanking regions of hSET1 and have shown that the sequences of hSET1 are unique to the malignant tumor tissues. The studies have been extended to the cultured cells and hSET1 has been shown to be differentially over-expressed in the malignant cells as compared to the normal cells at the RNA as well as protein level. The potential importance of these observations is underscored by our recently published studies showing complete regression of human colon cancer xenografts in nude-mice treated with phosphorothioate antisense to cause near complete depletion of SET1 in the animal. No significant adverse effects were seen, and all animals treated with antisense had regression of already established xenografts after i.p. injection of SET1 directed phosphorothioate antisense. In contrast, tumor progression was not affected by a paired scrambled antisense. These findings indicate that amplification by RT-PCR of specific circulating tumor-specific ribonucleotides may be a powerful tool for early detection of cancer, and perhaps a means for selecting patient-specific targeted therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4879.

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