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Singapore scientists said on Monday that they have identified a new gene, which is strongly associated with triple negative breast cancer (TNBC), a highly aggressive cancer that often has early relapse and metastasis following chemotherapy.
The newly identified biomarker, called RASAL2, is discovered by scientists at A*STAR's Genome Institute of Singapore (GIS), in collaboration with local clinicians and colleagues in the United States. Scientists said it provides a target for developing new therapeutics designed to treat this often deadly disease.
TNBC is deadly because it does not respond to targeted therapy like other breast cancers usually do, experts say.
Using breast cancer cell lines and genomic data from patient samples, molecular biologist Min Feng and her colleagues at the GIS adopted an integrated approach to search for genes whose deregulation may help explain the high metastatic potential of TNBC cells.
Feng found that a small Ribonucleic Acid(RNA), often called microRNA, is lost in highly metastatic TNBC cells but not in luminal breast cancer. As a result, RASAL2, which is negatively regulated by this microRNA, is up-regulated in a set of TNBC tumors. The study showed that TNBC patients whose tumors have high expression of RASAL2 tend to have a lower survival rate as compared to patients whose tumors have low levels of this gene. Additionally, the study showed that genetic knockdown of RASAL2 gene can lead to reduced metastasis in breast cancer mouse model.
"Cancer is an extremely heterogeneous disease, where many molecular processes have gone wrong in their own ways." Said Qiang Yu, project leader of the study. "Rather than a tumor suppresser, we show here that RASAL2 actually acts as a cancer promoting molecule in TNBC. This reminds us that the same molecule can function very differently in different subtypes of cancers, a phenomenon which has often been seen before."
The study is also a reflection of an adaptation towards translational research, Huck Hui Ng, GIS Executive Director explained.
"Because the laboratory findings do not always replicate the ' real world' of human tumors, validation with samples derived from actual human tumors remains the 'final proof' of whether novel laboratory findings can be applied to clinical practice."
Yu emphasized the necessity of further clinical validation for the study. He is also seeking industrial collaboration to develop diagnostic assays for high risk TNBC patients.
The findings were published recently in the Journal of Clinical Investigation (JCI).
