Novel Breast Cancer Gene Found

A new study identifies a gene that is especially active in aggressive subtypes of breast cancer. The research suggests that an overactive BCL11A gene drives triple-negative breast cancer development and progression. The research, which was done in human cells and in mice, provides new routes to explore targeted treatments for this aggressive tumour type. The findings were published in Nature Communications.

There are many types of breast cancers that respond differently to treatments and have different prognoses. Approximately one in five patients is affected by triple-negative breast cancer; these cancers lack three receptor proteins that respond to hormone therapies used for other subtypes of breast cancer. In recent years it has become apparent that the majority of triple-negative tumours are of the basal-like subtype.

Although new treatments are being explored, the prognosis for triple-negative cancer is poorer than for other types. To date, only a handful of genomic aberrations in genes have been associated with the development of triple-negative breast cancer.

The team looked at breast cancers from almost 3000 patients. Their search had a particular focus: they examined changes to genes that affect the behaviour of stem cells and developing tissues, because other work they have done suggests that such genes, when mutated, can often drive cancer development. Among these was BCL11A.

Higher activity of the BCL11A gene was found in approximately eight out of ten patients with basal-like breast cancer and was associated with a more advanced grade of tumour. In cases where additional copies of the BCL11A gene were created in the cancer, the prospects for survival of the patient were diminished.

When BCL11A was inactivated in an experimental system in mice, no mice developed tumours in the mammary gland, whereas all untreated animals developed tumours. The team also showed that BCL11A is required for normal development of breast stem cells and progenitors, which are thought to be the cells that, when mutated, give rise to basal-like breast cancer. 

This exciting result identifies a novel breast cancer gene in some of the more difficult-to-treat cases, and builds on work to develop a comprehensive molecular understanding of breast cancer that will inform clinical decisions and treatment choices. The team also propose that BCL11A is a strong candidate for development of a possible targeted treatment.
 
Originally posted by Wellcome Trust Sanger Institute.