Next-Generation Sequencing Uncovers Potential Genetic Drivers of Rare Breast Tumors


Key Points

  • Researchers used next-generation sequencing to identify genetic mutations in 15 phyllodes tumor samples (five benign, five borderline, and five malignant).
  • Two genes, EFGR and IFG1R, were amplified in multiple malignant phyllodes tumors.
  • A third gene, MED12, which is linked to gynecologic cancer, was frequently mutated in all kinds of phyllodes tumors.

A new study from researchers at the University of Michigan Comprehensive Cancer Center characterizes the genetic underpinnings of phyllodes tumors, a rare type of breast tumor. The study offers the first comprehensive analysis of the molecular alterations at work in these tumors, according to Cani et al, as reported in Molecular Cancer Research.

Analysis Details

The analysis used next-generation sequencing with a novel panel developed by ThermoFisher Scientific, called the Oncomine Cancer Research Panel, that allows researchers to identify alterations in more than 100 genes from archived tissue samples.

“We know little about the biology of phyllodes tumors. In part, they have not been studied much because it's difficult to accumulate a large number of samples. Using these new sequencing techniques, we were able to study archived tissue samples, which allowed us to identify enough samples to perform a meaningful analysis,” said study author Scott A. Tomlins, MD, PhD, Assistant Professor of Pathology and Urology at the University of Michigan Medical School.

Phyllodes tumors represent about 1% of all types of breast tumors. Most are benign, but they do have the potential to become metastatic. Currently, there are no reliable ways to predict which tumors are likely to recur or spread after initial treatment. Once phyllodes tumors become metastatic, there are few effective treatments.

Researchers looked at 15 samples of phyllodes tumors, pulled from archived tissue samples at the University of Michigan. The samples were equally divided according to their classification, with five considered benign, five borderline, and five malignant. While still a small sample, it can be sufficient with a rare tumor to identify genetic clues to the tumor’s biology. The researchers sequenced the samples against a panel of genes known to have some function or role in cancer.

Study Findings

Two genes, EGFR and IGF1R, were amplified in multiple malignant phyllodes tumors. Therapies have already been developed against EGFR and IGF1R proteins and tested in other cancers. Results from this study support evaluating these therapies in phyllodes tumors as well.

In addition, the researchers found the gene MED12 was frequently mutated in all classifications of phyllodes tumors. This gene also plays a role in some rare gynecologic tumors that are related to phyllodes tumors. The researchers believe MED12 could be involved with tumor initiation.

“Even though phyllodes tumors are rare, it’s important to have good treatment options for the aggressive cases. The first step is understanding the underlying biology of these tumors,” Dr. Tomlins said. “Further study and validation is needed, but our work has identified several promising targets involved in phyllodes tumors.”

Dr. Tomlins is the corresponding author for the Molecular Cancer Research article.

The study was supported by the A. Alfred Taubman Medical Research Institute at the University of Michigan. Dr. Tomlins has a separate sponsored research agreement with Compendia Bioscience/Life Technologies/ThermoFisher Scientific that provides access to the sequencing panel used in this study. No other aspect of the study was supported by the company.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.