Prognostic Biomarker Discovered for Aggressive Breast Cancer

A novel cancer gene has been discovered that, when overactive, triggers a particularly aggressive type of breast cancer to develop.

The oncogene was discovered using microarray technology, which allows large numbers of tissue samples to be tested simultaneously, picking up subtle differences in gene activity between normal cells and cancer cells.

Scientists, based at the Cambridge Research Institute, (Cambridge, UK), and at the British Columbia Cancer Agency (Vancouver, BC, Canada), tested patients tumors to see if the gene, called zinc finger protein 703 (ZNF703), is overactive could help identify patients with more aggressive tumors, so their treatment can be tailored accordingly. They studied the patterns of gene activity in 1,172 breast tumors, as well as breast cancer cells grown in the laboratory. This allowed them to eliminate one gene at a time until there was only one gene left within that region that was overactive in all the samples tested.

It is thought that up to a third of more aggressive estrogen positive breast cancers could have multiple copies of the ZNF703 gene. In the study, there were two patients in which ZNF703 was the only gene shown to be overactive, which provided further evidence that it was the driving force in the development of the cancer. An important observation that arises from the data is that amplification of the genes ZNF703 and erythroblastic leukemia viral oncogene homolog 2,(ERBB2), which are almost completely mutually exclusive, jointly account for around two-thirds of all breast cancers of the Luminal B subtype. This has potential for clinical application since a combination of immunohistochemistry and fluorescence in situ hybridization for these two genes/proteins (ZNF703 and ERBB2) can now be used to identify these more aggressive estrogen receptor positive (ER+) cancers in the clinic.

Dr. Lesley Walker, director of cancer information at Cancer Research UK, said, "This is the first gene of its kind to be discovered in breast cancer for five years. This is exciting because it is a prime candidate for the development of new breast cancer drugs designed specifically to target tumors in which this gene is overactive. Hopefully this will lead to more effective cancer treatments in the future." The study was published online on February 18, 2011, in the European Molecular Biology Organization (EMBO) Molecular Medicine.

Related Links:
Cambridge Research Institute
British Columbia Cancer Agency