ERBB2 and MED1 genes copy number variation in patients with breast cancer

Background: Recent studies have shown that about 50% of breast cancer patients with positive estrogen receptor (ER +) does not respond to hormone therapy orshow resistance to treatment after an initial successful response. Amplification and or overexpression of the ERBB2 (erb-b2 receptor tyrosine kinase2) gene have been reported to be in association with resistance to endocrine therapy. In addition, MED1(Mediator subunit 1) gene, co-activator of estrogen receptor, has been reported to be involved in tamoxifen resistance. However, the relationship between these two genes in regards to resistance to tamoxifen remains controversial. Since the twogenes, both are on chromosome 17q12, evaluation of these two genes amplificatin could be Indicative of the role of these genes in associated with resistance to tamoxifen. Methods: In this project, 65 tumors of breast cancer patients who were admitted to the cancer institute of Imam Khomeini Hospital were studied. Genomic copy number changes for selected genes were evaluated using MLPA (Multiplex Ligation-dependent Probe Amplification) technique. T-test was used for evaluation of possible association between ERBB2 and MED1 genes. Results: Amplification of ERBB2 and MED1 was seen in 17 and 13 samples, respectively. A significant correlation was seen between concomitant amplification of ERBB2 and MED1 genes (p = 0.028). Conclusion: Concomitant amplification of ERBB2 and MED1 genes can be used as a biomarker for sensivitivity or resistance to tamoxifen and provide a possible and novel therapeutic target for treatment of this category of patients.

Keywords:

Breast cancer , amplification , ERBB2 , MED1 , Tamoxifen