Gene mutation discovered in breast tumour
SINGAPORE scientists have uncovered a genetic mutation which makes it easier for doctors to recognise fibroadenomas (a common benign breast tumour).
This will help doctors avoid occasions when fibroadenomas may be misdiagnosed as breast cancer.
The breakthrough discovery happened after t he scientists discovered that the MED12 gene is frequently mutated in fibroadenomas, but very rarely in breast cancer. This gene mutated in 60 per cent of the 98 fibroadenomas they studied in Singapore. The discovery paves the way for a potential test in about three years’ time which will ease patient anxiety and reduce or remove the need for surgery for breast lumps found in these women. Possible drugs to treat this common tumour may be available in five to 10 years’ time.
About 20 scientists from multiple disciplines and organisations, including the National Cancer Centre Singapore (NCCS), DukeNUS Graduate Medical School Singapore (Duke-NUS) and Singapore General Hospital (SGH), studied fibroadenomas for a year before hitting the medical jackpot. The team’s findings have been published as a paper in the highly-regarded journal Nature Genetics.
Telling the difference
Currently, the best way to confirm if a patient has a fibroadenoma is to examine a tissue sample from the lesion under a microscope. While this form of examination is the gold standard in making a diagnosis, it is not always clear cut.
“Certain fibroadenomas may mimic breast cancers clinically and radiologically, so doctors sometimes face challenges in telling t hem apart,” said Professor Teh Bin Tean, Director and Principal Investigator at NCCS’ Laboratory of Cancer Epigenome.
Prof Teh, who is also a professor with Duke-NUS, reckoned that more researchers will continue to study the gene following the team’s discovery. Professor Patrick Tan of DukeNUS’ Cancer & Stem Cell Biology Program described the mutation as a litmus test for a benign breast tumour.
“While this gene is found to be frequently mutated i n
Certain fibroadenomas may mimic breast cancers clinically and radiologically, so doctors sometimes face challenges in telling them apart. While this gene is found to be frequently mutated in fibroadenomas, it almost never mutates in breast cancer.
fibroadenomas, it almost never mutates in breast cancer,” he said. He hopes the team’s findings will be validated independently by other groups.
The team will be continuing its own research into MED12, and aims to develop a reliable and robust laboratory test that can help in the diagnosis of breast tumours.
It will also study the gene’s function. “If we better understand the consequences of this mutation to MED12’s function, it will raise the possibility of developing medical treatments.”
Professor Tan Puay Hoon, Head and Senior Consultant at SGH’s Department of Pathology,
Professor Teh Bin Tean, Director and Principal Investigator at NCCS’ Laboratory of Cancer Epigenom
said: “It is amazing that these common breast t umours 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 fibroadenomas, this research can have many potential applications, including telling t hem apart from related but different breast tumours with diverse treatment strategies.”
Dr Benita Tan, Senior Consultant at SGH’s Department of General Surgery and the paper’s co-author, explained how such tumours are treated in the clinic. If the lumps are small and proven to be noncancerous, she is usually inclined to leave them alone, but surgery is needed for sizeable breast lumps, which can grow as big as 10cm across.
She said that similar MED12 mutations have been seen in uterine fibroids, another common benign tumour in women.
The paper’s lead author, Dr Lim Weng Khong, a Research Fellow at NCCS, said this suggests that the t wo types of tumours occurring in very different locations are related, and points to the possibility of a common cause.
“Now that we see this commonality of very distinct shared mutations between the breast and the uterus, we can infer that this could probably be related to abnormal responses to hormonal stimulation. Of course, this then generates questions and hypotheses for future studies,” he said.
Associate Professor Steven Rozen of Duke-NUS’ Cancer & Stem Cell Biology Program was also one of the lead investigators in the study.
What are fibroadenomas?
Fibroadenomas are the most common breast tumours in women of reproductive age. The benign condition affects one in 10 women worldwide, with about 3,000 cases in Singapore yearly.
Appearing as solid lumps that are usually painless, they vary in size and can grow over time or diminish on their own.
Doctors may monitor a fibroadenoma to detect changes, and may carry out biopsies to further evaluate the lump. Usually, such breast lumps do not require treatment, but if they are large and become uncomfortable, surgery may be needed to remove them.
What are uterine fibroids?
Uterine fibroids are growths of the uterus that develop from normal uterine smooth muscle cells that grow abnormally. Like fibroadenomas, fibroids are very common, non-cancerous, often appear during the child-bearing years, and there can be one or more.
They can be so tiny that they are not visible to the human eye, or grow so big that they can enlarge the uterus to the point that the woman looks pregnant.
Many women have uterine fibroids at some point in their lives, but most are unaware of these growths because there may not be any symptoms.
Clinical diagnosis is done via manual pelvic examination and ultrasound.
• This story was first published in Singapore Health, Nov-Dec 2014.