Methylation Profiling Defines an Extensive Field Defect in Histologically Normal Prostate Tissues Associated with Prostate Cancer
Prostate cancer (PCa) is typically found as a multifocal disease suggesting the potential for molecular defects within the morphologically normal tissue. The frequency and spatial extent of DNA methylation changes encompassing a potential field defect are unknown. A comparison of non-tumor-associate...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2013-04-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558613800474 |
| _version_ | 1831747806812962816 |
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| author | Bing Yang Sachin Bhusari Jessica Kueck Pushpa Weeratunga Jennifer Wagner Glen Leverson Wei Huang David F. Jarrard |
| author_facet | Bing Yang Sachin Bhusari Jessica Kueck Pushpa Weeratunga Jennifer Wagner Glen Leverson Wei Huang David F. Jarrard |
| author_sort | Bing Yang |
| collection | DOAJ |
| description | Prostate cancer (PCa) is typically found as a multifocal disease suggesting the potential for molecular defects within the morphologically normal tissue. The frequency and spatial extent of DNA methylation changes encompassing a potential field defect are unknown. A comparison of non-tumor-associated (NTA) prostate to histologically indistinguishable tumor-associated (TA) prostate tissues detected a distinct profile of DNA methylation alterations (0.2%) using genome-wide DNA arrays based on the Encyclopedia of DNA Elements 18 sequence that tile both gene-rich and poor regions. Hypomethylation (87%) occurred more frequently than hypermethylation (13%). Several of the most significantly altered loci (CAV1, EVX1, MCF2L, and FGF1) were then used as probes to map the extent of these DNA methylation changes in normal tissues from prostates containing cancer. In TA tissues, the extent of methylation was similar both adjacent (2 mm) and at a distance (>1 cm) from tumor foci. These loci were also able to distinguish NTA from TA tissues in a validation set of patient samples. These mapping studies indicate that a spatially widespread epigenetic defect occurs in the peripheral prostate tissues of men who have PCa that may be useful in the detection of this disease. |
| first_indexed | 2024-12-21T21:40:28Z |
| format | Article |
| id | doaj.art-729fc07f6a3e46289ccc47c1544f6f73 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-21T21:40:28Z |
| publishDate | 2013-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-729fc07f6a3e46289ccc47c1544f6f732022-12-21T18:49:22ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022013-04-0115439940810.1593/neo.13280Methylation Profiling Defines an Extensive Field Defect in Histologically Normal Prostate Tissues Associated with Prostate CancerBing Yang0Sachin Bhusari1Jessica Kueck2Pushpa Weeratunga3Jennifer Wagner4Glen Leverson5Wei Huang6David F. Jarrard7University of Wisconsin School of Medicine and Public Health, Madison, WIUniversity of Wisconsin School of Medicine and Public Health, Madison, WIUniversity of Wisconsin School of Medicine and Public Health, Madison, WIUniversity of Wisconsin School of Medicine and Public Health, Madison, WIUniversity of Wisconsin School of Medicine and Public Health, Madison, WIDepartment of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WIUniversity of Wisconsin Carbone Comprehensive Cancer Center, Madison, WIUniversity of Wisconsin School of Medicine and Public Health, Madison, WIProstate cancer (PCa) is typically found as a multifocal disease suggesting the potential for molecular defects within the morphologically normal tissue. The frequency and spatial extent of DNA methylation changes encompassing a potential field defect are unknown. A comparison of non-tumor-associated (NTA) prostate to histologically indistinguishable tumor-associated (TA) prostate tissues detected a distinct profile of DNA methylation alterations (0.2%) using genome-wide DNA arrays based on the Encyclopedia of DNA Elements 18 sequence that tile both gene-rich and poor regions. Hypomethylation (87%) occurred more frequently than hypermethylation (13%). Several of the most significantly altered loci (CAV1, EVX1, MCF2L, and FGF1) were then used as probes to map the extent of these DNA methylation changes in normal tissues from prostates containing cancer. In TA tissues, the extent of methylation was similar both adjacent (2 mm) and at a distance (>1 cm) from tumor foci. These loci were also able to distinguish NTA from TA tissues in a validation set of patient samples. These mapping studies indicate that a spatially widespread epigenetic defect occurs in the peripheral prostate tissues of men who have PCa that may be useful in the detection of this disease.http://www.sciencedirect.com/science/article/pii/S1476558613800474 |
| spellingShingle | Bing Yang Sachin Bhusari Jessica Kueck Pushpa Weeratunga Jennifer Wagner Glen Leverson Wei Huang David F. Jarrard Methylation Profiling Defines an Extensive Field Defect in Histologically Normal Prostate Tissues Associated with Prostate Cancer Neoplasia: An International Journal for Oncology Research |
| title | Methylation Profiling Defines an Extensive Field Defect in Histologically Normal Prostate Tissues Associated with Prostate Cancer |
| title_full | Methylation Profiling Defines an Extensive Field Defect in Histologically Normal Prostate Tissues Associated with Prostate Cancer |
| title_fullStr | Methylation Profiling Defines an Extensive Field Defect in Histologically Normal Prostate Tissues Associated with Prostate Cancer |
| title_full_unstemmed | Methylation Profiling Defines an Extensive Field Defect in Histologically Normal Prostate Tissues Associated with Prostate Cancer |
| title_short | Methylation Profiling Defines an Extensive Field Defect in Histologically Normal Prostate Tissues Associated with Prostate Cancer |
| title_sort | methylation profiling defines an extensive field defect in histologically normal prostate tissues associated with prostate cancer |
| url | http://www.sciencedirect.com/science/article/pii/S1476558613800474 |
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