Gene linked to aggressive breast cancer
UK scientists have linked an overactive gene to an aggressive type of breast cancer.
The team, from the Wellcome Trust Sanger Institute and the University of Cambridge, identified the BCL11A gene as especially active in ‘triple negative’ breast cancer – an aggressive form of the disease accounting for about one in five cases.
"This study is a promising step forward" - Dr Emma Smith, Cancer Research UK
Welcoming the findings – based on an analysis of cancer samples from almost 3000 women - Dr Emma Smith, senior science information officer at Cancer Research UK, said: “Figuring out the genes that play a role in triple negative breast cancer could lead to new ways to tackle the disease - so this study is a promising step forward.
“The next steps will be finding out if the gene plays the same role in causing breast cancer in women, and whether drugs can be developed to target the faulty molecules," she added.
Breast cancer is now known to exist in 10 distinct subtypes based on tumours’ genetic make-up. Most triple-negative breast cancer tumours are of a genetic type called ‘basal-like’.
BCL11A was found to be overactive in tumour samples from around eight in 10 patients with ‘basal-like’ disease.
Prognosis for triple negative cancers is poorer than for other forms, and limited knowledge of the distinct genetic properties of the disease has made the development of new treatments difficult.
Therapies used in treating other subtypes – such as trastuzumab and tamoxifen – do not work on this type of cancer, because tumour cells lack three different ‘receptor’ molecules that are targeted by the treatments.
In the new study, published in the journal Nature Communications, the researchers combed through existing databases of breast cancer samples, where gene changes had been analysed. In particular, they looked for changes to genes that affect the behaviour of stem cells – known to be involved in the development of breast cancer.
Dr Pentao Liu, senior author on the study, said BCL11A activity stood out as being particularly active in samples from triple negative cancers. “It had all the hallmarks of a novel breast cancer gene,” he said.
They then showed that adding extra copies of BCL11A to cells in the laboratory caused them to behave as cancer cells, and that blocking its activity led to lower rates of growth.
"Our studies in human cells clearly marked BCL11A as a novel driver for triple-negative breast cancers," added Dr Walid Khaled, co-author on the study.
Professor Carlos Caldas, from the Cancer Research UK Cambridge Institute, who led the work that categorised breast cancer into 10 subtypes, said the discover was ‘exciting’.
"It builds on our work to develop a comprehensive molecular understanding of breast cancer that will inform clinical decisions and treatment choices,”
The gene’s discovery should help in the discovery of new treatments, Caldas added.
- Khaled W.T., John Stingl, Xiongfeng Chen, H. Raza Ali, Oscar M. Rueda, Fazal Hadi, Juexuan Wang, Yong Yu, Suet-Feung Chin & Mike Stratton & (2015). BCL11A is a triple-negative breast cancer gene with critical functions in stem and progenitor cells, Nature Communications, 6 5987. DOI: http://dx.doi.org/10.1038/ncomms6987