Dataset Information

Tissue-of-origin-specific gene repositioning in breast and prostate cancer.

ABSTRACT: Genes have preferential non-random spatial positions within the cell nucleus. The nuclear position of a subset of genes differ between cell types and some genes undergo repositioning events in disease, including cancer. 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 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.

SUBMITTER: Meaburn KJ

PROVIDER: S-EPMC4795970 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Tissue-of-origin-specific gene repositioning in breast and prostate cancer.

Meaburn Karen J KJ Agunloye Olufunmilayo O Devine Michelle M Leshner Marc M Roloff Gregory W GW True Lawrence D LD Misteli Tom T

Histochemistry and cell biology 20160120 4

Genes have preferential non-random spatial positions within the cell nucleus. The nuclear position of a subset of genes differ between cell types and some genes undergo repositioning events in disease, including cancer. 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 ...[more]

PMID: 26791532

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Project description:BackgroundTypical high throughput microarrays experiments compare gene expression across two specimen classes - an experimental class and baseline (or comparison) class. The choice of specimen classes is a major factor in the differential gene expression patterns revealed by these experiments. In most studies of prostate cancer, histologically malignant tissue is chosen as the experimental class while normal appearing prostate tissue adjacent to the tumor (adjacent normal) is chosen as the baseline against which comparison is made. However, normal appearing prostate tissue from tumor free organ donors represents an alterative source of baseline tissue for differential expression studies.MethodsTo examine the effect of using donor normal tissue as opposed to adjacent normal tissue as a baseline for prostate cancer expression studies, we compared, using oligonucleotide microarrays, the expression profiles of primary prostate cancer (tumor), adjacent normal tissue and normal tissue from tumor free donors.ResultsStatistical analysis using Significance Analysis of Microarrays (SAM) demonstrates the presence of unique gene expression profiles for each of these specimen classes. The tumor v donor expression profile was more extensive that the tumor v adjacent normal profile. The differentially expressed gene lists from tumor v donor, tumor v adjacent normal and adjacent normal v donor comparisons were examined to identify regulated genes. When donors were used as the baseline, similar genes are highly regulated in both tumor and adjacent normal tissue. Significantly, both tumor and adjacent normal tissue exhibit significant up regulation of proliferation related genes including transcription factors, signal transducers and growth regulators compared to donor tissue. These genes were not picked up in a direct comparison of tumor and adjacent normal tissues.ConclusionsThe up-regulation of these gene types in both tissue types is an unexpected finding and suggests that normal appearing prostate tissue can undergo genetic changes in response to or in expectation of morphologic cancer. A possible field effect surrounding prostate cancers and the implications of these findings for characterizing gene expression changes in prostate tumors are discussed.

Dataset Information

Tissue-of-origin-specific gene repositioning in breast and prostate cancer.

Publications

Tissue-of-origin-specific gene repositioning in breast and prostate cancer.

Similar Datasets

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