Multi-disciplinary research team discovers that a gene known as MED12 is altered in nearly 60 percent of fibroadenomas
A multi-disciplinary team of scientists from the National Cancer Centre Singapore, Duke-NUS Graduate Medical School Singapore, and Singapore General Hospital have made a seminal breakthrough in understanding the molecular basis of fibroadenoma, one of the most common breast tumours diagnosed in women.
The team, led by Professors Teh Bin Tean, Patrick Tan, Tan Puay Hoon and Steve Rozen, used advanced DNA sequencing technologies to identify a critical gene called MED12 that was repeatedly disrupted in nearly 60% of fibroadenoma cases. Their findings have been published in the top-ranked journal Nature Genetics.
Fibroadenomas are the most common benign breast tumours in women of reproductive age, affecting thousands of women in Singapore each year. 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% of fibroadenomas.
Prof Tan Puay Hoon said, "It is amazing that these common breast tumours 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 research can have many potential applications."
Prof Tan added, "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 team's findings have also deepened the conceptual understanding of how tumours can develop. Like most breast tumours 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.
Assoc Prof Steve Rozen said, "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 tumour formation. Our study shows that far from that, fibroadenomas and possibly other tumours may actually arise from genetic lesions in stromal cells. Targeting such stromal cells may be an important avenue for therapy in the future."
Reflecting its importance, the study also sheds light on the cause of uterine fibroids, another common benign tumour in women where similar MED12 mutations have been observed. Prof Patrick Tan said, "Combined with our data, the fact that MED12 mutations are shared, highly frequent, and specific to fibroadenomas and uterine fibroids strongly attests to a role for abnormal responses to female hormones in the birth of these tumours."
The scientists are already planning further studies to explore this possibility by investigating the role of MED12 in other categories of breast tumours.
The study also involved investigators from the Cancer Science Institute of Singapore, Genome Institute of Singapore, A*STAR, and National University Hospital. According to Prof Teh Bin Tean, "Our study's success was only possible due to a multi-institutional, multi-disciplinary collaboration centred on the concept of team science. The group, called BRGO (Breast Research Group at Outram), leverages on the diverse expertise of scientists and clinicians coming from fields such as molecular biology, bioinformatics, pathology, breast surgery and oncology."
Funding for this work was provided by the Singapore National Medical Research Council, the Singapore Millennium Foundation, the Lee Foundation, the Tanoto Foundation, the National Cancer Centre Singapore's NCC Research Fund, the Duke-NUS Graduate Medical School, the Cancer Science Institute, Singapore and the Verdant Foundation, Hong Kong.
Lydia Ng | Eurek Alert!
Investigating cell membranes: researchers develop a substance mimicking a vital membrane component
25.05.2018 | Westfälische Wilhelms-Universität Münster
New approach: Researchers succeed in directly labelling and detecting an important RNA modification
30.04.2018 | Westfälische Wilhelms-Universität Münster
A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.
The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
23.07.2018 | Science Education
23.07.2018 | Health and Medicine
23.07.2018 | Life Sciences