PURPOSE: The MammaPrint™ gene signature, currently used in clinical practice, provides prognostic information regarding the recurrence and potential metastasis in breast cancer patients. However, the prognostic information of the 70 genes included can only be estimated at the RNA expression level. In this study, we investigated whether copy number information of MammaPrint™ genes at the DNA level can be used as a prognostic tool for breast cancer, as copy number variations (CNVs) are major contributors to cancer progression. METHODS: We performed CNV profiling of MammaPrint™ genes in 59 breast cancer cell lines and 650 breast cancer patients, using publicly available data in The Cancer Genome Atlas (TCGA) database. Statistical analyses including Fisher exact test, chi-square test, and Kaplan-Meier survival analyses were performed. RESULTS: All MammaPrint™ genes showed recurrent CNVs, particularly in TCGA cohort. CNVs of 32 and 36 genes showed significant associations with progesterone receptor and estrogen rector, respectively. No genes showed a significant association with human epidermal growth factor receptor 2 status and lymph node status. In addition, only six genes were associated with tumor stages. RFC4, HRASLS, NMU, GPR126, SCUBE2, C20orf46, and EBF4 were associated with reduced survival and RASSF7 and ESM1 were associated with reduced disease-free survival. CONCLUSION: Based on these findings, a concordance of CNV-based genomic rearrangement with expression profiling of these genes and their putative roles in disease tumorigenesis was established. The results suggested that the CNV profiles of the MammaPrint™ genes can be used to predict the prognosis of breast cancer patients. In addition, this approach may lead to the development of new cancer biomarkers at the DNA level.
Biomarkers ; Biomarkers, Tumor ; Breast Neoplasms* ; Breast* ; Carcinogenesis ; Cell Line ; Cohort Studies ; Disease-Free Survival ; DNA ; DNA Copy Number Variations ; Estrogens ; Genome ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Prognosis* ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone ; Recurrence ; RNA

Objective: To report the relationship of vegetation structure and environmental gradient and physiochemical properties of soil at Nikyal valley, Azad Jammu and Kashmir Methods: A survey of natural vegetation and soil of Nikyal valley was undertaken. Phytosociological survey was conducted by using Braun-Blanquet's approach. The study also investigated the vegetation structure and its relationship with altitude and edaphic factors. The floristic data was analyzed by cluster anlaysis, detrended correspondence analysis and canonical correspondence analysis using CANACOO 5.0. Results: A total of 110 plant species and 13 stands were merged into five major associations as dema rcated by cluster analysis and detrended correspondence analysis. The associations were Olea- Pinus- Themeda association, Myrsine- Rhus- Quercus association, Quercus- Rubus- Pinus association and Quercus association. Soil organic matter, saturation, pH and altitude play the major role in distribution of species. Conclusions: The variation in vegetation structure is controlled by the altitudinal gradient and physiochemical properties of soil. These results indicate a deteriorated forest structure and reduced regeneration pattern, demanding immediate attention of forest management authorities.