New Breast Cancer Gene Discovered
Researchers have long known that some breast cancers have a genetic link, but a new study appears to have found a gene that is particularly active in aggressive subtypes of breast cancer.
The gene, known as BCL11A, drives the development and progression of triple-negative breast cancer. These cancers account for one in five breast cancer cases and lack three receptor proteins that respond to hormone therapies used for other subtypes of breast cancer. Although new treatments are being explored, the prognosis for triple-negative cancer is poorer than for other subtypes.
The research team looked at breast cancers from almost 3000 patients. They were looking for changes to genes that affected the behavior of stem cells, because other research has suggested that such genes, when mutated, can drive cancer development.
"Our understanding of genes that drive stem cell development led us to search for consequences when these genes go wrong," says Dr Pentao Liu, senior author on the study, from the Wellcome Trust Sanger Institute. "BCL11A activity stood out because it is so active in triple-negative cancers. It had all the hallmarks of a novel breast cancer gene."
Approximately eight out of ten patients with basal-like breast cancer had increased activity of the BCL11A gene, and this activity was associated with a more advanced grade of tumor. In cases were additional copies of the BCL11A gene were created in the cancer in mice, the prospects for survival were diminished.
"Our gene studies in human cells clearly marked BCL11A as a novel driver for triple-negative breast cancers," says Dr Walid Khaled, joint first author on the study from the Wellcome Trust Sanger Institute and University of Cambridge. "We also showed that adding an active human BCL11A gene to human or mouse breast cells in the lab drove them to behave as cancer cells. As important, when we reduced the activity of BCL11A in three samples of human triple-negative breast cancer cells, they lost some characteristics of cancer cells and became less tumorigenic when tested in mice. So by increasing BCL11A activity we increase cancer-like behaviour; by reducing it, we reduce cancer-like behaviour."
When BCL11A was inactivated in mice, no mice developed tumors in the mammary gland, whereas all untreated animals developed tumors.
"This exciting result identifies a novel breast cancer gene in some of the more difficult-to-treat cases," 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. "It builds on our work to develop a comprehensive molecular understanding of breast cancer that will inform clinical decisions and treatment choices. Finding a novel gene that is active in cancer should also help in the search for new treatments." The team believes that BCL11A is a strong candidate for the development of a possible targeted treatment.