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Accession Number
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ADA567356
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Title
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Breast Cancer Diagnostics Based on Spatial Genome Organization.
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Publication Date
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Jul 2012
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Media Count
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19p
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Personal Author
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K. Meaburn T. Misteli
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Abstract
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Genomes are non-randomly organized within the cell nucleus. Importantly, individual gene loci undergo changes to their spatial position during disease, including cancer. We exploited, for the first time, these changes in spatial gene positioning as a novel tool for the detection of invasive breast cancer. Repositioning events in cancer cells are not a reflection of a global spatial genome reorganization and are instead gene- specific. Out of 20 genes we examined, 8 occupied significantly different intra- nuclear positions in breast cancer compared to normal tissues. Such genes serve as Gene Positioning Biomarkers (GPBs). We have demonstrated that these GPBs can accurately distinguish normal from cancer tissues. Crucially for a diagnostic test, these repositioning events were specific to cancer. There is little variation in the spatial positioning patterns of genes amongst normal individuals and most genes did not reposition in the benign breast diseases hyperplasia and fibroadenoma. We also adapted the approach to the requirements in a clinical setting by developing a normalized standard reference distribution for all GPB genes and by demonstrating that multiplexed combinatorial gene markers can further improve sensitivity and specificity. Our observations provide the first proof-of-principle that the spatial positioning of the genome can be used for diagnostic applications.
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Keywords
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Breast cancer
Cells(Biology)
Clinical medicine
Genes
Genome
Mammary glands
Neoplasms
Nuclei
Tissues(Biology)
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Source Agency
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Non Paid ADAS
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NTIS Subject Category
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57A - Anatomy
57S - Physiology
57E - Clinical Medicine
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Corporate Author
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The Geneva Foundation, Tacoma, WA.
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Document Type
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Technical report
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Title Note
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Final rept. 1 Sep 2008-30 Jun 2012.
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NTIS Issue Number
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1309
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Contract Number
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W81XWH-08-2-0098
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