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Tumor-Free Breast Tissue Can Have Increased Methylation

By Trevor | January 19, 2007

New research from a team at the Ohio State University Comprehensive Cancer Center shows that normal breast tissue as much as 4 cm away from a cancerous breast tissue can have increased methylation in the RASSF1A gene promoter.

During this study, the researchers measured the degrees of methylation in tissue removed from 47 patients who had undergone mastectomies for a form of breast cancer called invasive ductal carcinoma. This tissue was compared with 69 samples of normal tissue taken up to four centimeters (almost two inches) from the tumor’s visible edge and with control tissues removed during breast-reduction surgery.

The study also included two double-mastectomy cases in which both breasts had been removed to prevent cancer recurrence. For these, the researchers also tested tissue from four locations on the breast that had no visible tumor.

The researchers used microdissection techniques to isolate tiny milk ducts in each sample. They then measured methylation levels in the RASSF1A gene in epithelial cells that lined the ducts. These cells were the sources of the initial tumor.

As expected, tumor cells showed the highest methylation levels. But the researchers found significant methylation levels in normal tissue adjacent to the tumors in 29 patients. The degree of methylation was lower than in the tumor cells, but it was 1.75 times higher than in control cells.

“In both double-mastectomy cases, we were surprised to find high methylation levels in the tumor-free breast,” says Yan.

In addition, the researchers identified three other genes (called CYP26A1, KCNAB1 and SNCA) that were highly methylated in about one-third to nearly one-half of the breast tumors.

“Again to our surprise, we found that in 70 percent of cases, when these genes were highly methylated in tumor cells, they were also highly methylated in the adjacent normal tissue,” says Yan.

“This suggests that the presence of DNA methylation in normal tissue adjacent to tumors is more prevalent that previously thought.”

Link

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  • Methylation Markers Found for Multiple Cancers
  • Breast Cancer Detection Improves through Methylation-Specific PCR
  • The Friedreich ataxia GAA repeat expansion mutation induces comparable epigenetic changes in human and transgenic mouse brain and heart tissues.
  • Frequent epigenetic inactivation of hSRBC in gastric cancer and its implication in attenuated p53 response to stresses.


    • Topics: cancer, methylation, news links, research articles |

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