Project description:165 primary breast carcinomas were selected to study the gene expression profile in relation to the risk of developping local recurrence after breast conserving therapy; in addition 15 recurred tumors were profiled for comparison to their primary tumor.
Project description:Heterogeneity in global gene expression profiles between biopsy specimens taken peri-surgically from primary ER-positive breast carcinomas
Project description:Basal-like breast carcinoma is characterized by the expression of basal/myoepithelial markers, undifferentiated phenotype, highly aggressive behaviour and a frequent triple negative status (ESR-, PR-, Her2neu-). We have previously shown that epithelial-mesenchymal transition (EMT) occurs in basal-like breast tumours and identified Lysyl- Oxidase-Like 2 (LOXL2) as an EMT player and a poor prognosis marker in squamous cell carcinomas. We now show that LOXL2 mRNA is overexpressed in basal-like human breast carcinomas. Identification of new molecular markers in basal breast carcinomas
Project description:[original title] Metastatic Canine Mammary Carcinomas can be Identified by a Gene Expression Profile that partly Overlaps with Human Breast Cancer Profiles. Introduction: Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent. Methods: Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer. Results: Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors. Conclusions: Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs are in some aspects suitable as a translational model for human breast tumors in order to identify prognostic molecular signatures and potential therapeutic targets.
Project description:The Swedish haemangioma cohort consists of 17,200 women treated with radium-226 for skin haemangioma at an early age (<1.5 years of age) between 1920 and 1965. A total of 877 breast cancer cases were reported by December 2009, estimating an excess relative and absolute risk at the age of 50 years of 0.48 Gy^(−1) and 10.4 (10^4 PYR Gy)^(−1), respectively. We screened 31 primary breast carcinomas for genetic alterations using the OncoScan CNV Plus Assay to assess genomic instability.
Project description:Basal-like breast carcinoma is characterized by the expression of basal/myoepithelial markers, undifferentiated phenotype, highly aggressive behaviour and a frequent triple negative status (ESR-, PR-, Her2neu-). We have previously shown that epithelial-mesenchymal transition (EMT) occurs in basal-like breast tumours and identified Lysyl- Oxidase-Like 2 (LOXL2) as an EMT player and a poor prognosis marker in squamous cell carcinomas. We now show that LOXL2 mRNA is overexpressed in basal-like human breast carcinomas. Identification of new molecular markers in basal breast carcinomas 58 (IDC) infiltrative breast ductal carcinoma samples (Grade 3)
Project description:97 triple negative tumors were selected from the fresh-frozen tissue bank of the Netherlands Cancer Institute and gene expression profiles were generated using 35K oligonucleotide microarrays. Human breast carcinomas were snap frozen in liquid nitrogen within one hour after surgery and stored in the fresh-frozen tissue bank of the Netherlands Cancer Institute. RNA from a pool of more than 100 unselected fresh frozen breast carcinomas were isolated and pooled to form the reference to which each individual breast carcinoma is hybridized.
Project description:To find BRCA1-associated copy number abberations, the copy number profiles of Familial Basal-like BRCA1-mutated breast carcinomas were compared to Familial Basal-like carcinomas with no pathgogenic BRCA1/2 mutation. This led to the observation of unanticipated heterogeneity of the BRCA1 associated copy number profiles. Gene expression analysis on the same samples identified tumor infiltrating lymphocytes to be responsible for this observation. High number of infiltrating lymphocytes proved to be detrimental for copy number profiling efforts. After optimal sample selection, BRCA1-associated copy number abberations could be detected.
