Barrow TM, et al., 2015

Researchers in this study wanted to understand how changes in gene regulation might relate to certain types of breast cancer. They looked at something called "DNA methylation" in genes that are normally only active on one side of our DNA (either from mom or dad). When this methylation is disrupted, it can lead to abnormal cell behavior. The team found that these changes were much more common in breast cancer tissue than in healthy or benign tissue. Most interestingly, these abnormal patterns were often found in tumors that lacked hormone receptors like estrogen and progesterone, which are important for determining treatment and prognosis.

To better understand what’s normal, the researchers used healthy breast tissue from volunteers at the Komen Tissue Bank, the only biorepository of its kind that collects healthy breast tissue. These samples were critical for showing how different the cancerous tissues were. Thanks to these generous donors, the study could confirm that the gene changes were specific to cancer and not seen in healthy tissue or blood. This work may help explain how some breast cancers develop and why certain tumors behave more aggressively.

Full-Text Journal Article PubMed

What did they study?

In this study, researchers explored how certain genes, called imprinted genes, are regulated in breast tissue and how changes in their regulation might be linked to breast cancer. These imprinted genes are normally expressed from only one parent's DNA, and this control is managed through a process called DNA methylation. The team specifically investigated whether abnormal methylation in these genes was more common in people with invasive breast cancer and if those changes were connected to hormone receptor status, like estrogen and progesterone. By comparing breast tissue and blood samples from people with cancer, benign breast disease, and those without breast disease, the researchers aimed to uncover whether this type of epigenetic disruption could be a marker of more aggressive or harder-to-treat breast cancers.

What did they find?

• Frequent gene disruption in cancer tissue: Several imprinted genes showed abnormal DNA methylation in breast cancer samples, especially two regions of the IGF2 gene, which play a role in cell growth and have been linked to poor outcomes in other cancers.
• Stronger disruptions tied to more aggressive cancers: Tumors that lacked estrogen and progesterone receptors (often harder to treat) were significantly more likely to have multiple methylation abnormalities across these genes.
• Methylation changes were tissue-specific: These disruptions were seen only in breast tissue, not in blood, suggesting they are directly related to what's happening in the tumor itself.
• More “noise” in cancer DNA: Even in areas without clear disruptions, breast cancer tissue showed more variation in methylation patterns (like static in a signal) compared to healthy tissue, which could point to early warning signs of cancer development.
• Genes kept their one-sided expression—mostly: Despite all the changes in methylation, most of the imprinted genes still expressed from only one parental allele, suggesting that something deeper is maintaining this balance even in cancerous cells.

Why is this study important?

Full citation

Barrow TM,Barault L,Ellsworth RE,Harris HR,Binder AM,Valente AL,Shriver CD,Michels KB Aberrant methylation of imprinted genes is associated with negative hormone receptor status in invasive breast cancer.. International journal of cancer 2015 Aug; 137 (3). PMID:25560175.