Singapore scientists uncover gene associated with an aggressive breast cancer

PUBLIC RELEASE DATE:

30-Nov-2014

Contact: Tan Yun Yun tan_yun_yun@a-star.edu.sg 656-826-6273 Biomedical Sciences Institutes (BMSI)

Singapore--Scientists at A*STAR's Genome Institute of Singapore (GIS), in collaboration with local clinicians and colleagues in the USA, have identified a biomarker which is strongly associated with triple negative breast cancer (TNBC), a highly aggressive carcinoma that often has early relapse and metastasis following chemotherapy. The newly identified biomarker, a gene called RASAL2, provides a target for developing new therapeutics designed to treat this often deadly disease.

TNBC is deadly because, unlike other types of breast cancers such as estrogen receptor (ER) positive or HER2 amplified breast tumours which have effective targeted therapy, TNBC tumours do not respond to targeted therapy.

Breast cancer has many subtypes, each with its own genetic makeup. As such, different subtypes behave differently in invasion and metastasis. 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.

Dr Feng found that a small 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 tumours. The study showed that TNBC patients whose tumours have high expression of RASAL2 tend to have a lower survival rate as compared to patients whose tumours 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.

The findings were published recently in the Journal of Clinical Investigation (JCI).

Intriguingly, previous research found that RASAL2 was lost in some of the luminal type of breast tumours, where it acts as a tumour suppressor.

Project leader of the study, Prof Qiang Yu, Senior Group Leader of Cancer Therapeutics and Stratified Oncology Programme at the GIS, said, "Cancer is an extremely heterogeneous disease, where many molecular processes have gone wrong in their own ways. Rather than a tumour suppressor, 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."

Originally posted here:
Singapore scientists uncover gene associated with an aggressive breast cancer