A multi-disciplinary team of scientists from the National Cancer Centre Singapore, Duke-NUS Graduate Medical School Singapore, and Singapore General Hospital used advanced DNA sequencing technologies to identify a critical gene called MED12 that was repeatedly disrupted in nearly 60 per cent of fibroadenoma cases.
Fibroadenomas are the most common benign breast tumors in women of reproductive age, affecting thousands of women in Singapore each year, researchers said.
Worldwide, it is estimated that millions of women are diagnosed with fibroadenoma annually.
Frequently discovered in clinical workups for breast cancer diagnosis and during routine breast cancer screening, clinicians often face of challenge of distinguishing fibroadenomas from breast cancer.
To facilitate this diagnostic question, the team embarked on a study to identify if there are any genetic abnormalities in fibroadenomas that may be used to differentiate them.
By analysing all the protein-coding genes in a panel of fibroadenomas from Singapore patients, the team identified frequent mutations in a gene called MED12 in a remarkable 60 per cent of fibroadenomas.
"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," said study researcher Professor Tan Puay Hoon.
"Importantly, now that we know the cause of fibroadenoma, this research can have many potential applications," Hoon said.
The team's findings have also deepened the understanding of how tumors can develop.
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, using a technique called laser capture microdissection (LCM), showed that the pivotal MED12 mutations in fibroadenomas are found in the stromal cells.
"Stromal cells function to provide a supportive tissue around organs, and in breast cancers, are typically thought of as uninvolved or at least secondary bystanders in tumor formation," added study researcher Steve Rozen.
"Our study shows that far from that, fibroadenomas and possibly other tumors may actually arise from genetic lesions in stromal cells. Targeting such stromal cells may be an important avenue for therapy in the future," Rozen added.
The study is published in the journal Nature Genetics.