Triple-negative breast cancer: the answer is in the genes

Triple-negative breast cancer: the answer is in the genes

9 Jan 2015

A new study identifies a gene that is especially active in aggressive subtypes of breast cancer. The research, which was done in human cells and in mice, suggests that an overactive BCL11A gene drives triple-negative breast cancer development and progression.

The research provides new routes to explore targeted treatments for triple-negative cancer, where only a handful of genomic aberrations in genes have been associated with its development.

Sample from 3000 patients

The team looked at breast cancers from almost 3000 patients, examining changes to genes that affect the behavior of stem cells and developing tissues, as such genes, when mutated, can often drive cancer development. BCL11A was among the studied genes, whose alteration had consequences on cancer development. As Dr Pentao Liu, senior author on the study, from the Wellcome Trust Sanger Institute points out: “BCL11A activity stood out because it is so active in triple-negative cancers ".

Medical details: Reducing BCL11A’s activity means reducing cancer-like behavior

Higher activity of the BCL11A gene was found in approximately 8 out of 10 patients with basal-like breast cancer and was associated with a more advanced grade of tumor. In cases where additional copies of the BCL11A gene were created in the cancer, the prospects for survival of the patient were diminished, marking BCL11A as novel driver for triple-negative breast cancers.

This innovative research showed that adding an active human BCL11A gene to human or mouse breast cells in the lab drove them to behave as cancer. Equally important is that, when the activity of BCL11A was reduced in three samples of human triple-negative breast cancer cells, they lost some characteristics of cancer cells and became weaker in forming tumors when tested in mice. Consequently, increasing BCL11A activity means increasing cancer-like behavior, and reducing its activity means reducing cancer-like behavior.

Moreover, when BCL11A was inactivated in an experimental system in mice, no mice developed tumors in the mammary gland, whereas all untreated animals developed tumors.

“New routes for better clinical decisions and treatment choices”

"Finding an active novel gene in some of the most difficult-to-treat cancer cases should help in the search for new targeted treatments leading to better clinical decisions and treatment choices." says Professor Carlos Caldas, Professor of Cancer Medicine and Director of the Cambridge Breast Cancer Research Unit at the University of Cambridge, and Head of Breast Cancer Functional Genomics at Cancer Research UK Cambridge Institute.

 

Source: Wellcome Trust, Sanger Institute