Prostate Cancer Diagnostics and Prognostics Based on Interphase Spatial Genome Positioning
Technical Report,01 Jul 2012,31 Dec 2015
The Geneva Foundation Tacoma United States
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We are aiming to develop a novel strategy for the diagnosis and prognosis of prostate cancer. Our approach takes advantage of the non-random spatial organization of the genome in human cell nuclei. It is well established that individual gene loci can undergo changes in their spatial position during disease. We have previously exploited these changes in spatial positioning patterns as a novel tool for the detection of invasive breast cancer, and we are now extending these studies to prostate cancer. We have screened 48 genes in a panel of normal, cancer and hyperplasic human prostate tissues. We have identified three genes as potential prostate cancer biomarkers FLI1, MMP2 and MMP9, based on changes in their spatial positioning patterns in cancerous tissues, compared to normal. FLI1 and MMP9 repositioning is specific to cancer, and does not occur in benign disease. The positioning pattern of MMP2 is a biomarker for prostate disease in general, since MMP2 also repositions, albeit to a smaller degree, in benign disease. Changes in spatial positioning do not correlate with copy number changes or prognostic status. If validated, these three gene positioning biomarkers represent a novel class of biomarkers for the detection of prostate cancer and prostate disease. Further, we identified a fourth gene, SP100, which may have prognostic potential, since it repositions inlow grade Gleason score cancers, but not intermediate Gleason grade cancers.