Genes have preferential non-random spatial positions within the cell nucleus. The nuclear position of genes may differ between cell types and some genes undergo repositioning events in disease, including cancers. It is currently unclear whether the propensity of a gene to reposition reflects an intrinsic property of the locus or the tissue. Using quantitative FISH analysis of a set of genes which reposition in cancer, we test here the tissue-specificity of gene repositioning in normal and malignant breast or prostate tissues. We find tissue-specific organization of the genome in normal breast and prostate tissues with 40% of genes occupying differential positions between the two tissue types. While we demonstrate limited overlap between gene sets that repositioned in breast and prostate cancer, we identify two genes that undergo disease-related gene repositioning in both cancer types. Our findings indicate that gene repositioning in cancer is tissue-of-origin specific.

Background: The aim of this study was to evaluate whether pretest probability (PTP) assessment using the Diamond-Forrester Model (DFM) combined with coronary calcium scoring (CCS) can safely rule out obstructive coronary artery disease (CAD) and 30-day major adverse cardiovascular events (MACE) in acute chest pain patients. Methods: We retrospectively evaluated consecutive patients, age ≥18 years, with no known CAD, negative initial electrocardiogram, and troponin level. All patients had coronary computed tomographic angiography (CCTA) with CCS, and our final cohort consisted of 1988 patients. Obstructive CAD was defined as luminal narrowing of ≥50% in 1 or more vessels by CCTA. Patients were classified according to PTP as low (<10%), intermediate (10%–90%), or high (>90%). Results: The DFM classified 293 (14.7%), 1445 (72.7%), and 250 (12.6%) of patients as low, intermediate, and high risk, respectively, with corresponding 30-day MACE rates of 0.0%, 2.35%, and 14.8%. For patients with intermediate PTP and CCS ≤10, the negative predictive value was 99.2% (95% confidence interval: 98.7–99.8) for 30-day MACE while it was 92.62% (95% confidence interval: 87.9–97.3) for patients with high PTP. Among patients with a high PTP and CCS of zero, the prevalence of 30-day MACE and obstructive CAD remained high (7.07% and 10.1%, respectively). Conclusions: In acute chest pain patients without evidence of ischemia on initial electrocardiogram and cardiac troponin, low PTP by DFM or the combination of intermediate PTP and CCS ≤10 had excellent negative predictive values to rule out 30-day MACE. CCS is not sufficient to exclude obstructive CAD and 30-day MACE in patients with high PTP.

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