Project description:Brain metastatic disease occurs in 10-30% of metastatic breast cancer cases. The incidence of brain metastases is increasing with median overall survival < 2 years for patients. In order to better characterize oncogenic pathway activity pertinent to breast cancer brain metastasis, exome capture RNA sequencing was carried out on patient matched primary breast with brain metastatic tumor samples for 45 cases of breast cancer brain metastasis (N= 90 samples). Here, exome capture RNA sequencing data is deposited as sequencing batch corrected log2 transformed trimmed M of means (TMM) normalized counts per million (CPM) (log2(TMM-CPM +1) gene expression values (n=16,714 protein coding genes; N=90 tumor samples).
Project description:Brain metastatic disease occurs in 10-30% of metastatic breast cancer cases. The incidence of brain metastases is increasing with median overall survival < 2 years for patients. In order to better characterize oncogenic pathway activity pertinent to breast cancer brain metastasis, exome capture RNA sequencing was carried out on patient matched primary breast with brain metastatic tumor samples for 45 cases of breast cancer brain metastasis (N= 90 samples). Here, exome capture RNA sequencing data is deposited as sequencing batch corrected log2 transformed trimmed M of means (TMM) normalized counts per million (CPM) (log2(TMM-CPM +1) gene expression values (n=16,714 protein coding genes; N=90 tumor samples).
Project description:This SuperSeries is composed of the following subset Series: GSE14682: Metastatic breast cancer to the brain: set 1 GSE14683: Metastatic breast cancer to the brain: set 2 Refer to individual Series
Project description:Brain metastasis is one of the lethal causes of breast cancer. Here we identified an altered lipid metabolism state to be associated with brain metastatic potential of breast cancer cell lines. To investigate the mechanism, we knocked out genes mediating this altered state and examined transcriptomic changes. The results revealed that these genes confer cells a state with increased lipid and cholesterol biosynthesis and that resembles the lipid metabolite state seen in the brain. These findings revealed an unappreciated machinery that cancer cells adopt for their increased adaptability to the brain microenvironment.
Project description:In the present study we aimed to explore the role of tyrosine kinase receptor, RET, in promoting breast cancer brain metastasis. Using patient-derived brain metastatic models, we found RET significantly enriched in brain metastasis originating from estrogen receptor positive breast cancer where it played a key role in promoting cancer cell adhesion, survival, and outgrowth in the brain.
Project description:<p>Metastatic breast tumors must adapt to the metabolic constraints of their target tissues. To understand how tumor metabolism varies across sites, we compared glucose utilization in primary mammary fat pad (MFP) tumors and brain metastases derived from the breast cancer cell line MDA-MB-231. Tumors in each site displayed distinct patterns of metabolite labeling, reflecting differences in nutrient availability and biosynthetic activity. Brain tumors exhibited higher labeling of amino acids and TCA cycle intermediates, consistent with increased synthesis to overcome restricted nutrient access in the brain, whereas MFP tumors showed greater nucleotide synthesis activity. These findings illustrate how the tumor microenvironment shapes metabolic adaptation and highlight the flexible strategies cancer cells use to maintain growth in diverse tissues.</p>
Project description:Background: Metastases to the brain from breast cancer have a high mortality. Basal-like and HER2 positive breast cancers appear to have a high propensity to spread to the brain. The mechanisms that allow cells to colonise the brain are unclear. Methods: We have analysed matched and unpaired samples of breast cancer and brain metastases using morphology, immunophenotype and expression profiling and validated the data using in vitro cell culturing models and in vivo mice model. Results: Most of the brain metastases were triple negative and had a basal-like phenotype. Metastatic cells to the brain over-expressed HER3 compared to primaries and showed evidence of higher activation of the MAPK pathways. Inhibition using anti-neuregulin antibody, Herceptin and Lapatinib reduced tumour growth in vitro and in vivo. Conclusions: The data demonstrate activation of neuregulin-HER3 pathway in brain metastases from breast cancer and suggest that even in absence of HER2 amplification (as with triple negative and basal cancers), anti-epidermal growth factor receptor family inhibitors may have a role in treating these patients.
Project description:Background: Metastases to the brain from breast cancer have a high mortality. Basal-like and HER2 positive breast cancers appear to have a high propensity to spread to the brain. The mechanisms that allow cells to colonise the brain are unclear. Methods: We have analysed matched and unpaired samples of breast cancer and brain metastases using morphology, immunophenotype and expression profiling and validated the data using in vitro cell culturing models and in vivo mice model. Results: Most of the brain metastases were triple negative and had a basal-like phenotype. Metastatic cells to the brain over-expressed HER3 compared to primaries and showed evidence of higher activation of the MAPK pathways. Inhibition using anti-neuregulin antibody, Herceptin and Lapatinib reduced tumour growth in vitro and in vivo. Conclusions: The data demonstrate activation of neuregulin-HER3 pathway in brain metastases from breast cancer and suggest that even in absence of HER2 amplification (as with triple negative and basal cancers), anti-epidermal growth factor receptor family inhibitors may have a role in treating these patients