From a pool of more than 30,000 possibilities, researchers have identified 35 genes and three other molecules that most likely trigger one of the most aggressive forms of breast cancer, HER2+.

By narrowing what was once an overwhelming range of potential culprits to a relatively manageable number, the findings could dramatically increase the chances of identifying successful treatment approaches to this particularly pernicious form of breast cancer.

"In our investigation, we essentially went from thousands of genes and narrowed it down to 35 genes," said Ahmad Khalil, assistant professor at the Case Western Reserve University School of Medicine.

The investigators also uncovered three standout molecules called long intervening noncoding RNA (lincRNAs) that contribute to increased HER2 activity.

"For the first time, we have shown that these lincRNAs can also contribute to this HER2+ breast cancers," Khalil said.

"So we added another layer of complexity to the disease with lincRNAs. However, these lincRNAs could potentially open the door for RNA-based therapeutics in HER2+ breast cancer, a therapeutic strategy that has great potential but has not been fully tested in the clinic yet," Khalil noted.

In this study, the researchers chose an innovative approach that went beyond merely comparing gene expression in normal and in HER2+ cancer-affected breast tissue.

Instead, Khalil designed a study where the offending genes would stand out. He and colleagues compared gene expression differences among HER2+ breast cancer tissues of uncontrolled HER2 activity with those having greatly diminished HER2 activity.

Ultimately their work revealed 35 genes and three long intervening noncoding RNA (lincRNAs) molecules were most associated with the active HER2+ cells.