The genome is non-randomly organized within the three-dimensional space of the cell nucleus. The position of genomic regions can change during physiological process such as differentiation, development and disease. We hypothesize that we can exploit the changes in gene positioning patterns as indicators of disease and disease potential to develop a novel tool in the early detection of breast cancer and for the identification of pre-malignant cells with tumorigenic potential in normal tissue. This method offers particular promise for early detection or detection of pre-malignant precursor cells since changes in the positioning of specific genomic loci often occur before misexpression of a marker gene. We have characterized the positions of a selection of genes during normal and tumorigenic mammary epithelial differentiation using a 3D in vitro breast cancer model system. We have identified several genome markers which are differentially positioned during normal and tumorigenic differentiation. To test the feasibility of these genes for diagnostic purposes, we are comparing their positing patterns in normal and tumor breast tissues and we are defining a set of marker genes which exhibit differential positioning in malignant tissues.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA