Additional file 7: of The molecular landscape of premenopausal breast cancer

PARADIGM analysis in The Cancer Genome Atlas (TCGA). Table S1. Pathways detected by gene set enrichment analysis (GSEA) with input of gene expression and copy number variation data for the PARADIGM algorithm. The nine columns correspond to the pathway name, size of the pathway, Enrichment score (ES) score, Normalized enrichment score (NES) score, nominal p value, false discovery rate (FDR) q value, Family-wise error rate (FWER) p value, and leading edge (typical GSEA output). Table S2. Pathways detected by GSEA with input of gene expression, copy number variation and methylation data for the PARADIGM algorithm. The nine columns correspond to the pathway name, the size of pathway, ES score, NES score, nominal p value, FDR q value, FWER p value, and leading edge (typical GSEA output). (XLSX 88 kb

Additional file 12: of The molecular landscape of premenopausal breast cancer

Supplementary methods. This file contains additional details of the analyses. (DOCX 36 kb

Additional file 11: of The molecular landscape of premenopausal breast cancer

Gene list for clustering premenopausal (preM) estrogen receptor-positive (ER+) tumors. Table S1. Gene list selected by sparse k-means algorithm in The Cancer Genome Atlas (TCGA) data. Table S2. Genes selected based on TCGA data that are also in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) data for validation. Table S3. Fixed number of genes (n = 21), gene list being selected from sparse k-means in TCGA. Table S4. Gene list selected by semi-supervised algorithm in METABRIC. Table S5. Fixed number of genes (n = 21), gene list being selected by semi-supervised algorithm in TCGA. Table S6. Genes (n = 28) in the LumA cluster that are significantly different between clusters 1 and 3. (XLSX 37 kb

BRCA1 deficiency in ovarian cancer is associated with alteration in expression of several key regulators of cell motility – A proteomics study

<p>Functional loss of expression of breast cancer susceptibility gene 1(<i>BRCA1</i>) has been implicated in genomic instability and cancer progression. There is emerging evidence that <i>BRCA1</i> gene product (BRCA1) also plays a role in cancer cell migration. We performed a quantitative proteomics study of EOC patient tumor tissues and identified changes in expression of several key regulators of actin cytoskeleton/cell adhesion and cell migration (CAPN1, 14-3-3, CAPG, PFN1, SPTBN1, CFN1) associated with loss of BRCA1 function. Gene expression analyses demonstrate that several of these proteomic hits are differentially expressed between early and advanced stage EOC thus suggesting clinical relevance of these proteins to disease progression. By immunohistochemistry of ovarian tumors with BRCA1^+/+ and BRCA1^null status, we further verified our proteomic-based finding of elevated PFN1 expression associated with BRCA1 deficiency. Finally, we established a causal link between PFN1 and BRCA1-induced changes in cell migration thus uncovering a novel mechanistic basis for BRCA1-dependent regulation of ovarian cancer cell migration. Overall, findings of this study open up multiple avenues by which BRCA1 can potentially regulate migration and metastatic phenotype of EOC cells.</p

TCGA Expedition Directory Structure.

<p>TCGA Expedition Directory Structure.</p

TCGA Expedition Modules and associated TCGA Datatypes managed.

<p>TCGA Expedition Modules and associated TCGA Datatypes managed.</p

Architecture of the Pittsburgh Genome Resource Repository.

<p>Architecture of the Pittsburgh Genome Resource Repository.</p