Expression data from primary breast tumors
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE27830 | GEO | 2017/01/17
SECONDARY ACCESSION(S): PRJNA137893
REPOSITORIES: GEO
Similar Datasets
Project description:Introduction: CHEK2 is a moderate penetrance breast cancer risk gene, whose truncating mutation 1100delC increases the risk about two fold. We pursued to investigate gene copy number aberrations and gene expression profiles that are typical for breast tumors of CHEK2 1100delC mutation carriers. Materials and methods: A total of 126 breast tumor tissue specimens including 32 samples from patients carrying CHEK2 1100delC were studied in array comparative genomic hybridization (aCGH) and gene expression experiments (GEX). After dimensionality reduction with CGHregions R package, CHEK2 1100delC associated regions in the aCGH data were detected by Wilcoxon rank sum test. Linear model was fitted to GEX data with R package limma. Genes whose expression levels were associated with CHEK2 1100delC mutation were detected by Bayesian method. Results: We discovered four lost and three gained CHEK2 1100delC related loci. These include losses of 1p13.3-31.3, 8p21.1-2, 8p23.1-2 and 17p12-13.1 as well as gains of 12q13.11-3, 16p13.3 and 19p13.3. Twenty-eight genes located on these regions showed differential expression between CHEK2 1100delC and other tumors nominating them as candidates for CHEK2 1100delC associated tumor progression drivers. These included CLCA1 on 1p22 as well as CALCOCO1, SBEM and LRP1 on 12q13. Altogether 188 genes were differentially expressed between CHEK2 1100delC and other tumors. Of these, 144 had elevated and 44 lowered expression levels. Our results suggest WNT pathway as a driver of tumorigenesis in breast tumors of CHEK2 1100delC mutation carriers and a role for the olfactory receptor protein family in cancer progression. Differences in the expression of the 188 CHEK2 1100delC associated genes divided breast tumor samples from three independent datasets into two groups that differed in their relapse-free survival time. Conclusions: We have shown that copy number aberrations of certain genomic regions are associated with CHEK2 mutation 1100delC. On these regions we have identified potential drivers of CHEK2 1100delC associated tumorigenesis, whose role in cancer progression is worth investigating. Furthermore, poorer survival related to the CHEK2 1100delC gene expression signature highlights pathways that are likely to have a role in the development of metastatic disease in carriers of CHEK2 1100delC mutation. 78 samples from breast tumors: 13 tumors from CHEK2 1100delC mutation carriers, 65 other tumors
2011-05-10 | E-GEOD-24697 | biostudies-arrayexpress
Project description:Abstract Introduction: CHEK2 is a moderate penetrance breast cancer risk gene, whose truncating mutation 1100delC increases the risk about two fold. We pursued to investigate gene copy number aberrations and gene expression profiles that are typical for breast tumors of CHEK2 1100delC mutation carriers. Materials and methods: A total of 126 breast tumor tissue specimens including 32 samples from patients carrying CHEK2 1100delC were studied in array comparative genomic hybridization (aCGH) and gene expression experiments (GEX). After dimensionality reduction with CGHregions R package, CHEK2 1100delC associated regions in the aCGH data were detected by Wilcoxon rank sum test. Linear model was fitted to GEX data with R package limma. Genes whose expression levels were associated with CHEK2 1100delC mutation were detected by Bayesian method. Results: We discovered four lost and three gained CHEK2 1100delC related loci. These include losses of 1p13.3-31.3, 8p21.1-2, 8p23.1-2 and 17p12-13.1 as well as gains of 12q13.11-3, 16p13.3 and 19p13.3. Twenty-eight genes located on these regions showed differential expression between CHEK2 1100delC and other tumors nominating them as candidates for CHEK2 1100delC associated tumor progression drivers. These included CLCA1 on 1p22 as well as CALCOCO1, SBEM and LRP1 on 12q13. Altogether 188 genes were differentially expressed between CHEK2 1100delC and other tumors. Of these, 144 had elevated and 44 lowered expression levels. Our results suggest WNT pathway as a driver of tumorigenesis in breast tumors of CHEK2 1100delC mutation carriers and a role for the olfactory receptor protein family in cancer progression. Differences in the expression of the 188 CHEK2 1100delC associated genes divided breast tumor samples from three independent datasets into two groups that differed in their relapse-free survival time. Conclusions: We have shown that copy number aberrations of certain genomic regions are associated with CHEK2 mutation 1100delC. On these regions we have identified potential drivers of CHEK2 1100delC associated tumorigenesis, whose role in cancer progression is worth investigating. Furthermore, poorer survival related to the CHEK2 1100delC gene expression signature highlights pathways that are likely to have a role in the development of metastatic disease in carriers of CHEK2 1100delC mutation. 79 samples from breast tumors: 22 tumors from CHEK2 1100delC mutation carriers, 57 other tumors Five files attached represent segmented values, copy number calls, gain, loss and normal copy number probabilities.
2011-05-10 | E-GEOD-24698 | biostudies-arrayexpress
Project description:Elevated Met receptor tyrosine kinase (RTK) expression correlates with poor outcome in breast cancer, yet a causal role for Met in the development of breast cancer has not been directly established. To examine this question, we generated a transgenic mouse model that targets expression of an oncogenic Met receptor (MetMut) to the mammary epithelium. We show that MetMut induces mammary tumors with a variety of histopathologies that exhibit gene expression profiles sharing similarities with human basal and luminal breast tumor subtypes. Among all breast cancers, we further demonstrate that the Met receptor is primarily overexpressed in human basal and HER2 positive breast cancers, and that a Met associated gene expression signature identifies patients with poor prognosis. Experiment Overall Design: Common reference design. 26 samples (including 20 normal tissue and 32 tumor tissue samples) replicated twice as dye swaps, generating a total of 52 arrays.
2009-04-03 | E-GEOD-10450 | biostudies-arrayexpress
Project description:Luminal breast cancers express estrogen (ER) and/or progesterone (PR) receptors and respond to hormone therapies. Basal-like “triple negative” (TN) cancers lack steroid receptors but are cytokeratin (CK) 5-positive and require chemotherapy. Here we show that over half of primary ER+PR+ breast cancers contain an ER–PR–CK5+ “luminobasal” subpopulation exceeding 1% of cells. Starting from ER+PR+ luminal cell lines, we generated novel lines with varying luminal to luminobasal-cell ratios and studied their molecular and biological properties. In luminal disease, luminobasal cells expand in response to antiestrogen or estrogen withdrawal therapies. The phenotype and gene signature of the hormone resistant cells matches that of clinical TN basal-like and claudin-low disease. Luminobasal-cell expansion in response to hormone therapies is regulated by Notch1 signaling and can be blocked by gamma-secretase inhibitors (GSI). Our data establish a previously unrecognized plasticity of ER+PR+ luminal breast cancers that, without genetic manipulation, mobilizes outgrowth of hormone-resistant basal-like disease in response to treatment. This undesirable outcome can be prevented by combining endocrine therapies with Notch inhibition. 24 array samples
2011-12-21 | E-GEOD-31870 | biostudies-arrayexpress
Project description:Introduction: CHEK2 is a moderate penetrance breast cancer risk gene, whose truncating mutation 1100delC increases the risk about two fold. We pursued to investigate gene copy number aberrations and gene expression profiles that are typical for breast tumors of CHEK2 1100delC mutation carriers. Materials and methods: A total of 126 breast tumor tissue specimens including 32 samples from patients carrying CHEK2 1100delC were studied in array comparative genomic hybridization (aCGH) and gene expression experiments (GEX). After dimensionality reduction with CGHregions R package, CHEK2 1100delC associated regions in the aCGH data were detected by Wilcoxon rank sum test. Linear model was fitted to GEX data with R package limma. Genes whose expression levels were associated with CHEK2 1100delC mutation were detected by Bayesian method. Results: We discovered four lost and three gained CHEK2 1100delC related loci. These include losses of 1p13.3-31.3, 8p21.1-2, 8p23.1-2 and 17p12-13.1 as well as gains of 12q13.11-3, 16p13.3 and 19p13.3. Twenty-eight genes located on these regions showed differential expression between CHEK2 1100delC and other tumors nominating them as candidates for CHEK2 1100delC associated tumor progression drivers. These included CLCA1 on 1p22 as well as CALCOCO1, SBEM and LRP1 on 12q13. Altogether 188 genes were differentially expressed between CHEK2 1100delC and other tumors. Of these, 144 had elevated and 44 lowered expression levels. Our results suggest WNT pathway as a driver of tumorigenesis in breast tumors of CHEK2 1100delC mutation carriers and a role for the olfactory receptor protein family in cancer progression. Differences in the expression of the 188 CHEK2 1100delC associated genes divided breast tumor samples from three independent datasets into two groups that differed in their relapse-free survival time. Conclusions: We have shown that copy number aberrations of certain genomic regions are associated with CHEK2 mutation 1100delC. On these regions we have identified potential drivers of CHEK2 1100delC associated tumorigenesis, whose role in cancer progression is worth investigating. Furthermore, poorer survival related to the CHEK2 1100delC gene expression signature highlights pathways that are likely to have a role in the development of metastatic disease in carriers of CHEK2 1100delC mutation.
2011-05-10 | GSE24698 | GEO
Project description:Introduction: CHEK2 is a moderate penetrance breast cancer risk gene, whose truncating mutation 1100delC increases the risk about two fold. We pursued to investigate gene copy number aberrations and gene expression profiles that are typical for breast tumors of CHEK2 1100delC mutation carriers. Materials and methods: A total of 126 breast tumor tissue specimens including 32 samples from patients carrying CHEK2 1100delC were studied in array comparative genomic hybridization (aCGH) and gene expression experiments (GEX). After dimensionality reduction with CGHregions R package, CHEK2 1100delC associated regions in the aCGH data were detected by Wilcoxon rank sum test. Linear model was fitted to GEX data with R package limma. Genes whose expression levels were associated with CHEK2 1100delC mutation were detected by Bayesian method. Results: We discovered four lost and three gained CHEK2 1100delC related loci. These include losses of 1p13.3-31.3, 8p21.1-2, 8p23.1-2 and 17p12-13.1 as well as gains of 12q13.11-3, 16p13.3 and 19p13.3. Twenty-eight genes located on these regions showed differential expression between CHEK2 1100delC and other tumors nominating them as candidates for CHEK2 1100delC associated tumor progression drivers. These included CLCA1 on 1p22 as well as CALCOCO1, SBEM and LRP1 on 12q13. Altogether 188 genes were differentially expressed between CHEK2 1100delC and other tumors. Of these, 144 had elevated and 44 lowered expression levels. Our results suggest WNT pathway as a driver of tumorigenesis in breast tumors of CHEK2 1100delC mutation carriers and a role for the olfactory receptor protein family in cancer progression. Differences in the expression of the 188 CHEK2 1100delC associated genes divided breast tumor samples from three independent datasets into two groups that differed in their relapse-free survival time. Conclusions: We have shown that copy number aberrations of certain genomic regions are associated with CHEK2 mutation 1100delC. On these regions we have identified potential drivers of CHEK2 1100delC associated tumorigenesis, whose role in cancer progression is worth investigating. Furthermore, poorer survival related to the CHEK2 1100delC gene expression signature highlights pathways that are likely to have a role in the development of metastatic disease in carriers of CHEK2 1100delC mutation.
2011-05-10 | GSE24697 | GEO
Project description:This microarray dataset contains 51 triple-negative breast cancers with clinical and recurrence information for at least 3 years of follow-up and 106 luminal breast cancers (reanalyzed data from Series GSE24124, GSE9309, and GSE17040). A novel set of 45-gene signature that was statistically predictive of distant metastasis recurrence for triple-negative breast cancer was identified in this study.
2012-11-01 | GSE33926 | GEO
Project description:Luminal breast cancers express estrogen (ER) and/or progesterone (PR) receptors and respond to hormone therapies. Basal-like “triple negative” (TN) cancers lack steroid receptors but are cytokeratin (CK) 5-positive and require chemotherapy. Here we show that over half of primary ER+PR+ breast cancers contain an ER–PR–CK5+ “luminobasal” subpopulation exceeding 1% of cells. Starting from ER+PR+ luminal cell lines, we generated novel lines with varying luminal to luminobasal-cell ratios and studied their molecular and biological properties. In luminal disease, luminobasal cells expand in response to antiestrogen or estrogen withdrawal therapies. The phenotype and gene signature of the hormone resistant cells matches that of clinical TN basal-like and claudin-low disease. Luminobasal-cell expansion in response to hormone therapies is regulated by Notch1 signaling and can be blocked by gamma-secretase inhibitors (GSI). Our data establish a previously unrecognized plasticity of ER+PR+ luminal breast cancers that, without genetic manipulation, mobilizes outgrowth of hormone-resistant basal-like disease in response to treatment. This undesirable outcome can be prevented by combining endocrine therapies with Notch inhibition.
2011-12-21 | GSE31870 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE24697: Breast tumors from CHEK2 1100delC mutation carriers: genomic landscape and clinical implications (GEX) GSE24698: Breast tumors from CHEK2 1100delC mutation carriers: genomic landscape and clinical implications (CGH) Refer to individual Series
2011-05-10 | E-GEOD-24707 | biostudies-arrayexpress
Project description:The telomeric amplicon at 8p12 is common in ER+ breast cancers. Array-CGH and expression analyses of 1172 tumors revealed ZNF703/Zeppo1 was the single gene within the minimal amplicon and was amplified predominantly in the Luminal B subtype. Amplification was shown to correlate with increased gene and protein expression and was associated with a distinct expression signature and poor outcome. In the luminal MCF-7 cell line manipulation of ZNF703 expression altered transcription of genes also present within the primary tumor signature, including TGFBR2 (whose promoter was bound by ZNF703). Overexpression of ZNF703 rendered MCF-7 cells insensitive to TGFβ-induced suppression of mammosphere formation. Forced overexpression of ZNF703 in normal human breast epithelial cells enhanced the frequency of in vitro colony-forming cells from luminal progenitors. Together these data strongly point to ZNF703/Zeppo1 as a novel oncogene in Luminal B breast cancer.
2011-03-27 | GSE23673 | GEO