Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Ovarian Cancer CGH

ABSTRACT: OBJECTIVES: Amplification of the 11q13 locus is commonly observed in a number of human cancers including both breast and ovarian cancer. Cyclin D1 and EMS1 have been implicated as candidate oncogenes involved in the emergence of amplification at this locus. Detailed analysis of the 11q13 amplicon in breast cancer led to the discovery of four regions of amplification suggesting the involvement of other genes. Here, we investigate the role of EMSY, a recently described BRCA2 interacting protein, as a key element of the 11q13 amplicon in ovarian cancer. EMSY maps to 11q13.5 and is amplified in 13% of breast and 17% of ovarian carcinomas. METHODS: EMSY amplification was assessed by fluorescent in-situ hybridization (FISH) in 674 ovarian cancers in a tissue microarray and correlated with histopathological subtype and tumor grade. A detailed map of the 11q13 amplicon in 51 cases of ovarian cancer was obtained using cDNA-array-based comparative genomic hybridization (aCGH). To further characterize the role of EMSY within this amplicon, we evaluated both the amplification profiles and RNA expression levels of EMSY and two other genes from the 11q13 amplicon in an additional series of 22 ovarian carcinomas. : EMSY amplification was seen in 52/285 (18%) high grade papillary serous carcinomas, 4/27 (15%) high grade endometrioid carcinomas, 3/38 (8%) clear cell carcinomas, and 3/10 (30%) undifferentiated carcinomas. aCGH mapping of 11q13 in ovarian cancer showed that EMSY localized to the region with the highest frequency of copy number gain. Cyclin D1 and EMS1 showed a lower frequency of copy number gain. A highly significant correlation between EMSY gene amplification and RNA expression was also observed (P = 0.0001). This was a stronger correlation than for other genes at 11q13 including Cyclin D1 and PAK1. CONCLUSIONS: These findings support the role of EMSY as a key oncogene within the 11q13 amplicon in ovarian cancer. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Keywords: Logical Set Using regression correlation

ORGANISM(S): Homo sapiens

SUBMITTER: Hanna Kim

PROVIDER: E-GEOD-16408 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Amplification of EMSY, a novel oncogene on 11q13, in high grade ovarian surface epithelial carcinomas.

Brown Lindsay A LA Irving Julie J Parker Robin R Kim Hanna H Press Joshua Z JZ Longacre Teri A TA Chia Stephen S Magliocco Anthony A Makretsov Nikita N Gilks Blake B Pollack Jonathan J Huntsman David D

Gynecologic oncology 20051019 2

<h4>Objectives</h4>Amplification of the 11q13 locus is commonly observed in a number of human cancers including both breast and ovarian cancer. Cyclin D1 and EMS1 have been implicated as candidate oncogenes involved in the emergence of amplification at this locus. Detailed analysis of the 11q13 amplicon in breast cancer led to the discovery of four regions of amplification suggesting the involvement of other genes. Here, we investigate the role of EMSY, a recently described BRCA2 interacting pro ...[more]

PMID: 16236351

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Project description:Summary: Breast cancer cell lines have been used widely to investigate breast cancer pathobiology and new therapies. Breast cancer is a molecularly heterogeneous disease, and it is important to understand how well and which cell lines best model that diversity. In particular, microarray studies have identified molecular subtypes (luminal A, luminal B, ERBB2-associated, basal-like and normal-like) with characteristic gene-expression patterns and underlying DNA copy number alterations (CNAs). Here, we studied a collection of breast cancer cell lines to catalog molecular profiles and to assess their relation to breast cancer subtypes. Whole-genome DNA microarrays were used to profile gene expression and CNAs in a collection of 52 widely-used breast cancer cell lines, and comparisons were made to existing profiles of primary breast tumors. Hierarchical clustering was used to identify gene-expression subtypes, and Gene Set Enrichment Analysis (GSEA) to discover biological features of those subtypes. Genomic and transcriptional profiles were integrated to discover within high-amplitude CNAs candidate cancer genes with coordinately altered gene copy number and expression. Transcriptional profiling of breast cancer cell lines identified one luminal and two basal-like (A and B) subtypes. Luminal lines displayed an estrogen receptor (ER) signature and resembled luminal-A/B tumors, basal-A lines were associated with ETS-pathway and BRCA1 signatures and resembled basal-like tumors, and basal-B lines displayed mesenchymal and stem-cell characteristics. Compared to tumors, cell lines exhibited similar patterns of CNA, but an overall higher complexity of CNA (genetically simple luminal-A tumors were not represented), and only partial conservation of subtype-specific CNAs. We identified 80 high-level DNA amplifications and 13 presumptive homozygous deletions, and the resident genes with concomitantly altered gene-expression, highlighting known and novel candidate breast cancer genes. Overall, breast cancer cell lines were genetically more complex than tumors, but retained expression patterns with relevance to the luminal-basal subtype distinction. The compendium of molecular profiles defines cell lines suitable for investigations of subtype-specific pathobiology, biomarkers and therapies, and provides a resource for discovery of new breast cancer genes. HEEBO oligonucleotide microarrays from the Stanford Functional Genomics Facility were used to perform gene expression profiling of 50 human breast epithelial cell lines, in comparison to a universal RNA reference. Expression data were analyzed by hierarchical clustering to identify subgroups, and gene set enrichment analysis to identify subgroup-specific gene pathways.

Project description:The first goal of the study was to find the genes that explain the difference in progression of age-related retinal degeneration (ageRD) between the inbred strains C57BL/6J-c2J (B6a) and BALB/cByJ (C). The specific goal was to find the candidate genes that explain the chromosome 6 and chromosome 10 quantitative trait loci (QTL) found in a previous study. Genes differentially expressed in retina between both strains and that map to the QTL are candidate genes. By integrating different approaches: microarray study, knowledge-based candidate gene search and screening of genetic variants, we found 35 candidate genes for chromosome 6 QTL and 14 candidate genes for chromosome 10 QTL. Five genes for each QTL were selected for sequencing and qPCR analysis. One gene, Tnfaip3 was selected for phenotypic testing and was excluded as the quantitative trait gene for chr10 QTL. The second goal of the study was to find biological processes and pathways associated with ageRD by Gene Ontology analysis of the microarray data. We concentrated on GO terms overrepresented in either strain at 8 months; the age when there is a difference in the phenotype (outer nuclear layer thickness). The GO analysis revealed that transcripts associated with inflammation, mitochondrial envelope, DNA repairing and oxidative stress were increased in the ageRD sensitive C strain with age (8 months). In the ageRD resistant B6a strain transcripts associated with antioxidant response, regulation of blood vessel size and growth factor activity were increased with age. Transcripts associated with cell remodeling and lipid metabolism were increased in either strain with age. This study aims to identify gene expression differences in posterior eyecups between the strains C and B6a at 4 months and at 8 months. Twelve animals were used per strain and time point for a total of 48 mice. Total RNA for 3 animals (6 eyes) were pooled giving a total of 4 biological replicates per strain and time point. The 4-month C samples labeled with Cy5 were hybridized with the 4-month B6a samples labeled with Cy3 (4 biological replicates); the 8-month C samples labeled with Cy5 were hybridized with the 8-month B6a samples labeled with Cy3, for 8 arrays (4 biological replicates). A second set of eight arrays were used to analyzed the same RNA samples but with the dye orientation reversed, yielding a total of 16 arrays in the experiment. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc.

Dataset Information

Ovarian Cancer CGH

Publications

Amplification of EMSY, a novel oncogene on 11q13, in high grade ovarian surface epithelial carcinomas.

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