In breast cancers, the genetic abnormalities arise from the epithelial cells (dark areas). The scientists showed that the pivotal MED12 mutations in fibroadenomas are found in the stromal cells (light areas).

In diagnosing breast lumps, clinicians face the challenge of distinguishing benign tumours like fibroadenomas (pictured above) from malignant ones.

By using advanced DNA sequencing technologies and analysing all the protein coding genes in a series of fibroadenomas from Singapore patients, a team from SGH, NCCS and Duke-NUS found recurrent mutations in MED12, a critical gene, in almost 60% of fibroadenoma cases.

This landmark discovery was achieved by a multi-institutional and multidisciplinary team led by Professors Teh Bin Tean, Patrick Tan, Tan Puay Hoon and Steve Rozen. The group started a study to find genetic abnormalities in fibroadenomas that may help differentiate them from other tumours.

Explained Professor Tan Puay Hoon, Head of SGH’s Department of Pathology and Chair of the SingHealth Duke-NUS Pathology Academic Clinical Program, “What this discovery means for patients is that the MED12 gene mutation can be used as an additional tool to help confirm a benign diagnosis of fibroadenoma especially in small tissue samples.   This can relieve anxiety and avoid surgery for patients.”

Said Dr Benita Tan, Senior Consultant at the SingHealth Duke-NUS Breast Centre, “Fibroadenomas may commonly form lumps that are usually harmless. However, some with indeterminate clinical and radiological features need to be further studied to differentiate them from malignant tumours.”

“The MED12 gene mutation can be used as an additional tool to help confirm a benign diagnosis … This can relieve anxiety and avoid surgery for patients.”
Prof Tan Puay Hoon, Head, SGH Pathology

By studying the gene, the team discovered that fibroadenomas grow differently from breast cancers, deepening the current understanding of how tumours develop.   The study also sheds light on the cause of uterine fibroids, another common benign tumour in women where similar MED12 mutations have been observed.   The scientists are planning further studies to investigate the role of MED12 in other categories of breast tumours.

“We hope to produce a diagnostic gene test based on our research finding in two to three years’ time and find, in five to ten years’ time, a drug that targets the MED12 gene and resolves benign breast lumps,” added Prof Patrick Tan of the Duke-NUS Cancer & Stem Cell Biology Program.

Prof Teh Bin Tean of the same Duke- NUS Program who is also Director and Principal Investigator, Laboratory of Cancer Epigenome at NCCS, said, “Our group, who are members of the Breast Research Group at Outram (BRGO), leverages on the diverse expertise of scientists and clinicians from fields such as molecular biology, bioinformatics, pathology, breast surgery and oncology. We have been able to work well based on mutual trust and a strong conviction that drives our common vision to focus on cancers prevalent in Asia.”

Said Dr Lim Weng Khong, a Research Fellow in NCCS, “The nature of the group’s research is such that a lot of coordination has to be done between different institutions and professions. In fact, it is quite an achievement that our 22 members could work so well yet informally in our team science collaboration.”

“Our team believes in the importance of focusing on cancers found in Asia that have not been studied widely. Hence, we work with other institutions in the region,” added Prof Rozen.

Other than being involved in the BRGO, Prof Teh, along with Duke-NUS’ Cancer & Stem Cell Biology Program’s Profs Patrick Tan and Steve Rozen have been making news with their prolific cancer research output.   These include their discovery in 2013 of a potent carcinogen in herbal remedies and significant breakthroughs in understanding the cause and development of bile duct cancer.   Prof Teh has also worked with other researchers to identify a new form of deadly lymphoma that is found mainly in Asia.   Results of the fibroadenoma study were published in Nature Genetics, August 2014.