New Gene Identified That Drives Triple-Negative Breast Cancer

A novel gene has been discovered that, when mutated, can drive development and progression of triple-negative breast cancer which is an aggressive form of the disease that accounts for 10% to 20% of breast cancers.

Triple-negative breast cancer (TNBC) has poor prognostic outcome compared with other types of breast cancer and the molecular and cellular mechanisms underlying TNBC pathology are not fully understood.

An international team of scientists led by those at the Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK) assessed alterations to genes that influence the actions of stem cells and developing tissues, as past studies from the team has indicated that these alterations affect cancer development. By assessing these gene alterations among breast cancer cells from nearly 3,000 patients, the team found that a gene called B-cell lymphoma/leukemia 11A (BCL11A) was particularly active in triple-negative breast cancer.

The team used both a mouse model and human cells and various techniques to identify the gene. Ribonucleic acid (RNA) from sorted cells was extracted using PicoPure RNA isolation kit (Molecular Devices; Sunnyvale, CA, USA) and real-time polymerase chain reactions (PCR) were run in ABI-7900HT (Applied Biosystems; Foster City, CA, USA) in triplicate. Immunohistochemistry was carried using a fluorescence Axiophot microscope (Zeiss; Oberkochen, Germany).

Increased BCL11A activity was identified in around eight out of 10 basal-like breast cancers and was associated with more aggressive tumors. What is more, when the team reduced BCL11A activity in three samples of human triple-negative breast cancer cells, they found that these cells lost some cancer-like characteristics. When these cells were introduced to mice, they were less likely to drive tumor growth. The team found that BCL11A is important for the normal development of breast stem cells and progenitor cells. Past studies have shown that mutations in these cells may drive the development of basal-like cancers.

Walid Khaled, PhD, the lead author of the study said, “Our gene studies in human cells clearly marked BCL11A as a novel driver for triple-negative breast cancers. By increasing BCL11A activity we increase cancer-like behavior; by reducing it, we reduce cancer-like behavior.” The study was published on January 9, 2015, in the journal Nature Communications.

Related Links:
Wellcome Trust Sanger Institute
Molecular Devices
Applied Biosystems