Much of gene research is over my head, but the discovery of a new breast cancer oncogene, ZNF703, is exciting. It appears to have been discovered by two independent research groups (references below) and published alongside one another in the same journal EMBO Molecular Medicine today this past week.
The only other breast oncogene that I am aware of is Her2 which has been very helpful in identifying which patients are most likely to respond to Herceptin. This greatly helps in tailoring therapy to the individual.
The first group of researcher scientists used ‘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.
The researchers had already identified a region on human chromosome eight likely to harbor genes linked to the development of a more aggressive form of estrogen positive breast cancer, because multiple copies of it are commonly found in tumors but not in healthy tissue.
Focusing on this region, they studied the patterns of gene activity in 1172 breast tumors, as well as breast cancer cells grown in the lab. 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.
The second group specifically studied Luminal B breast cancers which represent a fraction of ER-positive tumors associated with poor recurrence-free and disease-specific survivals in all adjuvant systemic treatment categories including hormone therapy alone.
Using mass spectrometry, they identified ZNF703 as a cofactor of a nuclear complex comprising DCAF7, PHB2, and NCOR2. ZNF703 expression results in the activation of stem-cell related genes expression leading to an increase in cancer stem cells.
They were able to show that ZNF703 is implicated in the regulation of estrogen receptor and E2F1 transcription factor which points to the prominent role of ZNF703 in transcription modulation, stem cell regulation and luminal B oncogenesis.
ZNF703 is a common Luminal B breast cancer oncogene that differentially regulates luminal and basal progenitors in human mammary epithelium; Carroll JS, Curtis C, Aparicio S, Caldas C, et al; EMBO Molecular Medicine, Article first published online: 18 FEB 2011; DOI: 10.1002/emmm.201100122
ZNF703 gene amplification at 8p12 specifies luminal B breast cancer; Sircoulomb F, Nicolas N, et al; EMBO Molecular Medicine, Article first published online: 18 FEB 2011; DOI: 10.1002/emmm.201000121
Cancer Research UK Press Release, February 18, 2011