Critical Gene Altered in Numerous Fibroadenoma Patients

Advanced DNA sequencing technologies have been used to identify a critical gene that was repeatedly disrupted in nearly 60% of fibroadenoma cases.

Frequently discovered in clinical workups for breast cancer diagnosis and during routine breast cancer screening, clinicians often face the challenge of distinguishing fibroadenomas from breast cancer.

A multidisciplinary team of scientists from the National Cancer Center Singapore (Singapore) and their colleagues studies a total of 98 fibroadenoma tumors of which 12 were from fresh-frozen tumors and a further 86 were from archival formalin-fixed paraffin-embedded (FFPE) samples. Tumors and whole blood were obtained from patients undergoing surgical excision of fibroadenoma.

The team used a variety of molecular techniques including a technique called laser capture microdissection (LCM). Fresh-frozen fibroadenomas were embedded in optimal cutting temperature (OCT) compound and 8 μm-thick sections were cut using a microtome cryostat. Stained slides were then loaded onto the laser capture microscope stage. The ArcturusXT Laser Capture Microdissection (LCM) System and a Capsure Macro LCM cap (Life Technologies, Grand Island, NY, USA) were then placed automatically over the chosen area of the tissue.

By analyzing all the protein-coding genes in a panel of fibroadenomas from the patients, the team identified frequent mutations in a gene called Mediator Complex Subunit 12 (MED12) in a remarkable 60% of fibroadenomas. Like most breast tumors including breast cancers, fibroadenomas consist of a mixed population of different cell types, called epithelial cells and stromal cells. However, unlike breast cancers where the genetic abnormalities arise from the epithelial cells, the scientists showed that the pivotal MED12 mutations in fibroadenomas are found in the stromal cells using the LCM technique.

Patrick Tan, MD, PhD, a professor and a lead author of the study said, “It is amazing that these common breast tumors can be caused by such a precise disruption in a single gene. Our findings show that even common diseases can have a very exact genetic basis. Importantly, now that we know the cause of fibroadenoma, this study can have many potential applications. For example, measuring the MED12 gene in breast lumps may help clinicians to distinguish fibroadenomas from other types of breast cancer. Drugs targeting the MED12 pathway may also be useful in patients with multiple and recurrent fibroadenomas as this could help patients avoid surgery and relieve anxiety.” The study was published on July 20, 2014, in the journal Nature Genetics.

Related Links:
National Cancer Center Singapore
Life Technologies, Grand Island