AsianScientist (Oct. 15, 2015) – Using whole exome and targeted sequencing, a team of researchers from the SingHealth Duke-NUS Academic Medical Center has uncovered the genetic landscape of a distinct breast tumor group called fibroepithelial tumors. Their study, published in Nature Genetics, identifies the genes behind the formation and progression of these tumors, potentially improving the diagnostic accuracy of breast cancer screening and enhancing clinical intervention for patients with such tumors.
Fibroepithelial tumors are a distinct breast tumor group which includes two tumor types: fibroadenomas and phyllodes tumors. Fibroadenomas are the most common benign breast tumors in women of reproductive age, with thousands of women in Singapore and millions worldwide estimated to be diagnosed with fibroadenomas every year.
Last year, the team identified novel MED12 mutations in the majority of fibroadenomas, a finding that was also reported in Nature Genetics. Now, they have charted the genetic landscape for fibroadenomas as well as phyllodes tumors, another subtype of fibroepithelial tumors that have both benign and cancerous forms, the latter accounting for about two percent of breast cancers in Singapore.
“Breast cancer is the leading cancer affecting women in Singapore. By shedding light on the genetic landscape of fibroepithelial breast tumors, we can delve deeper into how they are formed, their possible progression into cancer, and determine how to manage them,” said Professor Teh Bin Tean, Deputy Director (Research), National Cancer Center Singapore (NCCS), a co-principal investigator (PI) of the study.
Currently, distinguishing fibroadenomas from phyllodes tumors can be challenging to clinicians. The tumors can also progress from benign into malignant forms, and recur even after surgical removal. A deeper understanding into their formation and progression is thus important for the accurate diagnoses and treatment of such tumors, and for breast cancer care.
The team performed exome sequencing of 22 phyllodes tumors and targeted sequencing of 100 fibroepithelial tumors to uncover the genes responsible for their formation and progression. They found that mutations in MED12 and another gene called RARA were common in both fibroadenomas and phyllodes tumors, with the mutation in RARA thought to enhance its binding to co-repressors and lower the transcription of RARA-targeted genes.
The researchers also identified a suite of mutations more common in phyllodes tumors, which could potentially be used as biomarkers.
“In pathology, we see challenging cases where fibroadenomas and phyllodes tumors are not clearly distinguishable. The discovery of their causative genes brings hope that we can eventually test for the presence of culprit genes to identify these breast tumor types accurately. Patients can then receive appropriate clinical intervention in a timely manner,” said Professor Tan Puay Hoon, Head and Senior Consultant, Department of Pathology, Singapore General Hospital (SGH) and co-PI of the study.
The findings also provide candidate therapeutic targets for fibroepithelial tumors, paving the way for alternative treatment options. Currently, there is no effective therapy for phyllodes tumors apart from surgery.
“This discovery unleashes tremendous potential for the treatment of fibroepithelial breast tumors. Other than surgery, drugs targeting the tumors’ gene pathway could help to treat them or prevent recurrence, which is not uncommon among patients with these tumors,” said Professor Patrick Tan from the Duke-NUS Graduate Medical School Cancer and Stem Cell Biology Program and co-PI of the study.
The article can be found at: Tan J et al. (2015) Genomic Landscapes of Breast Fibroepithelial Tumors.
Source: SingHealth; Photo: Shutterstock.
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