Leshner Marc, Devine Michelle, Roloff Gregory W, True Lawrence D, Misteli Tom, Meaburn Karen J
National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Department of Pathology, University of Washington, Seattle, WA 98195.
Mol Biol Cell. 2016 Jan 15;27(2):236-46. doi: 10.1091/mbc.E15-05-0280. Epub 2015 Nov 12.
Genes occupy preferred spatial positions within interphase cell nuclei. However, positioning patterns are not an innate feature of a locus, and genes can alter their localization in response to physiological and pathological changes. Here we screen the radial positioning patterns of 40 genes in normal, hyperplasic, and malignant human prostate tissues. We find that the overall spatial organization of the genome in prostate tissue is largely conserved among individuals. We identify three genes whose nuclear positions are robustly altered in neoplastic prostate tissues. FLI1 and MMP9 position differently in prostate cancer than in normal tissue and prostate hyperplasia, whereas MMP2 is repositioned in both prostate cancer and hyperplasia. Our data point to locus-specific reorganization of the genome during prostate disease.
基因在间期细胞核内占据特定的空间位置。然而，定位模式并非基因座的固有特征，基因可根据生理和病理变化改变其定位。在此，我们筛选了40个基因在正常、增生性和恶性人类前列腺组织中的径向定位模式。我们发现前列腺组织中基因组的整体空间组织在个体间基本保守。我们鉴定出三个基因，其在肿瘤性前列腺组织中的核定位发生了显著改变。与正常组织和前列腺增生相比，FLI1和MMP9在前列腺癌中的定位不同，而MMP2在前列腺癌和增生中均发生了重新定位。我们的数据表明前列腺疾病期间基因组存在基因座特异性重组。
