Copy number and expression analysis of FOSL1, GSTP1, NTSR1, FADD and CCND1 genes in primary breast tumors with axillary lymph node metastasis

Abstract

In breast cancer, lymph node (LN) metastasis is one of the strongest prognostic factors at diagnosis. Therefore the identification of molecular markers with metastatic potential that promote the development of LN metastasis is of critical clinical relevance. In this study, we evaluated the copy number status of the FOSL1, GSTP1, NTSR1, FADD and CCND1 genes by TaqMan assays in 137 breast cancer patients, 84 with LN metastasis (LN+) and 53 with no LN metastasis (LN-). The copy number data for four of these genes (FOSL1, GSTP1, FADD and CCND1) were integrated with their mRNA expression levels in 31 patients. In both groups of patients, gains were the most frequent copy number alteration (CNA) observed, involving mainly the CCND1, NTSR1 and FADD genes; mRNA overexpression was more commonly observed for the CCND1 and FADD genes. For the FADD gene in the LN+ group, gene expression was shown to be dependent on CNAs; for the other genes no association was found. In conclusion, increase copy number and mRNA overexpression of FOSL1, GSTP1, FADD, NTSR1 and CCND1 genes are frequently observed in primary breast tumors, and except for the FADD gene, they occur independently and irrespectively of the patients' LN axillary metastatic status.

Keywords: Breast cancer; DNA copy number; gene expression; lymph node; metastasis.