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Identifying the molecular signature of the t(12;14) subgroup of uterine leiomyomata using a paired analysis

ABSTRACT: Uterine leiomyomata (UL), the most common neoplasm in reproductive age women, have recurrent cytogenetic abnormalities including t(12;14). To develop a molecular signature, matched t(12;14) and non-t(12;14) tumors identified by FISH or karyotyping from each of 9 women were profiled using Affymetrix GeneChip U133 Plus 2.0 oligonucleotide arrays. Model analysis demonstrated the necessity for a matched design to eliminate the confounding effect of genotype and environment that underlay patient to patient variation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE18096 | GEO | 2012/03/09

SECONDARY ACCESSION(S): PRJNA119385

REPOSITORIES: GEO

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Identifying the molecular signature of the t(12;14) subgroup of uterine leiomyomata using a paired analysis

Project description:Uterine leiomyomata (UL), the most common neoplasm in reproductive age women, have recurrent cytogenetic abnormalities including t(12;14). To develop a molecular signature, matched t(12;14) and non-t(12;14) tumors identified by FISH or karyotyping from each of 9 women were profiled using Affymetrix GeneChip U133 Plus 2.0 oligonucleotide arrays. Model analysis demonstrated the necessity for a matched design to eliminate the confounding effect of genotype and environment that underlay patient to patient variation. Matched myometrium, t(12;14) fibroid tumors and non-t(12;14) fibroid tumors identified by FISH or karyotyping from each of 9 women were profiled using Affymetrix GeneChip U133 Plus 2.0 oligonucleotide gene expression arrays.

2012-03-09 | E-GEOD-18096 | biostudies-arrayexpress

Identifying the molecular signature of the interstitial del(7q) subgroup of uterine leiomyomata using a paired analysis

Project description:Uterine leiomyomata (UL), the most common neoplasm in reproductive-age women, have recurrent cytogenetic abnormalities including del(7)(q22q32). To develop a molecular signature, matched del(7q) and non-del(7q) tumors identified by FISH or karyotyping from 11 women were profiled with expression arrays. Our analysis using paired t-tests demonstrates this matched design is critical to eliminate confounding effects of genotype and environment that underlie patient variation. A gene list ordered by genome-wide significance showed enrichment for the 7q22 target region. Modification of the gene list by weighting each sample for percent of del(7q) cells to account for the mosaic nature of these tumors further enhanced the frequency of 7q22 genes. Pathway analysis revealed two of the 19 significant functional networks were associated with development and the most represented pathway was protein ubiquitination, which can influence tumor development by stabilizing oncoproteins and destabilizing tumor suppressor proteins. Array CGH (aCGH) studies determined the only consistent genomic imbalance was deletion of 9.5 megabases from 7q22-7q31.1. Combining the aCGH data with the del(7q) UL mosacism-weighted expression analysis resulted in a list of genes that are commonly deleted and whose copy number is correlated with significantly decreased expression. These genes include the proliferation inhibitor HPB1, the loss of expression of which has been associated with invasive breast cancer, as well as the mitosis integrity-maintenance tumor suppressor RINT1. This study provides a molecular signature of the del(7q) UL subgroup and will serve as a platform for future studies of tumor pathogenesis. Keywords: uterine leiomyomata, fibroids, del(7)(q22q32), gene expression, aCGH, microarray

2009-08-17 | GSE12814 | GEO

Transcription profiling of human uterine leiomyomata - identifying the molecular signature of the interstitial del(7q) subgroup using a paired analysis

Project description:Uterine leiomyomata (UL), the most common neoplasm in reproductive-age women, have recurrent cytogenetic abnormalities including del(7)(q22q32). To develop a molecular signature, matched del(7q) and non-del(7q) tumors identified by FISH or karyotyping from 11 women were profiled with expression arrays. Our analysis using paired t-tests demonstrates this matched design is critical to eliminate confounding effects of genotype and environment that underlie patient variation. A gene list ordered by genome-wide significance showed enrichment for the 7q22 target region. Modification of the gene list by weighting each sample for percent of del(7q) cells to account for the mosaic nature of these tumors further enhanced the frequency of 7q22 genes. Pathway analysis revealed two of the 19 significant functional networks were associated with development and the most represented pathway was protein ubiquitination, which can influence tumor development by stabilizing oncoproteins and destabilizing tumor suppressor proteins. Array CGH (aCGH) studies determined the only consistent genomic imbalance was deletion of 9.5 megabases from 7q22-7q31.1. Combining the aCGH data with the del(7q) UL mosacism-weighted expression analysis resulted in a list of genes that are commonly deleted and whose copy number is correlated with significantly decreased expression. These genes include the proliferation inhibitor HPB1, the loss of expression of which has been associated with invasive breast cancer, as well as the mitosis integrity-maintenance tumor suppressor RINT1. This study provides a molecular signature of the del(7q) UL subgroup and will serve as a platform for future studies of tumor pathogenesis. Experiment Overall Design: Matched del(7q) and non-del(7q) tumors identified by FISH or karyotyping from each of eleven woman were profiled using Affymetrix GeneChip U133 Plus 2.0 oligonucleotide gene expression arrays.

2009-08-22 | E-GEOD-12814 | biostudies-arrayexpress

Characterization of Plexiform Leiomyomata Provide Further Evidence for Genetic Heterogeneity Underlying Uterine Fibroids

2008-05-01 | GSE9511 | GEO

Transcription profiling of human Plexiform Leiomyomata provide further evidence for genetic heterogeneity underlying uterine fibroids

Project description:Plexiform leiomyomata are a histologically defined subgroup of benign uterine smooth muscle tumors based on their epitheliod cytology and abundant extracellular matrix. We used microarrays to compare plexiform leiomyomata to normal myometrium (smooth muscle of the uterine wall), typical leiomyomata, cellular or atypical leiomyomata and malignant leiomyosarcoma of the uterus. Experiment Overall Design: Samples analyzed on U133 Plus 2.0 and HuFL (GPL570 and GPL80). Experiment Overall Design: Data from the microarrays was merged by selection data for probe sets in which Entrez gene ID code on the GPL570 table equaled the Entrez gene ID on the GPL80 table. Experiment Overall Design: If more than one row on the GPL570 matched the value of the Entrez gene ID for a probe set on the GPL80 table, the values from the GPL570 were averaged. Thus, the GPL570 data was condensed to conform to the GPL80 format. Experiment Overall Design: The reformated raw data from both microarrays was then normalized such that the sum of the expression values was 3 million, and that values less than 20 were subsequently set to 20 (to permit log transformation in some statistical analysis).

2008-06-16 | E-GEOD-9511 | biostudies-arrayexpress

Human Uterine Leiomyomata microRNA gene expression

Project description:MicroRNAs (miRNAs) are a class of small, non-coding RNAs. MiRNAs regulate developmental activity and may be aberrantly expressed in human diseases, including cancer. Expression of miRNAs is tissue or organ specific. Human uterine leiomyomas (ULMs) are the most common neoplasms of women, characterized by the ovarian sex hormone dependence, worse morbidity in black women and genetic heterogeneity. The high incidence of the disease may be associated with developmental defects in uteri. In this study, we examined miRNA expression in 55 ULMs with matched myometrium using spotted microarray platform. Keywords: Disease state analysis

2007-04-15 | GSE5244 | GEO

Expression data from normal myometrium, leiomyomata, and leiomyosarcomas

Project description:The molecular etiology of uterine leiomyosarcoma (ULMS) is poorly understood, which accounts for the wide disparity in outcomes among women with this disease. We examined and compared the molecular profiles of ULMS, fibroids, and normal myometrium (NL) to identify clinically relevant molecular subtypes. RNA was hybridized to Affymetrix U133A 2.0 transcription microarrays. Differentially expressed genes and pathways were identified using standard methods.

2015-01-08 | GSE64763 | GEO

Identifying the molecular signature of the interstitial deletion 7q subgroup of uterine leiomyomata using a paired analysis.

Project description:Uterine leiomyomata (UL), the most common neoplasm in reproductive-age women, have recurrent cytogenetic abnormalities including interstitial deletion of 7q. To develop a molecular signature, matched del(7q) and non-del(7q) tumors identified by FISH or karyotyping from 11 women were profiled with expression arrays. Our analysis using paired t tests demonstrates this matched design is critical to eliminate the confounding effects of genotype and environment that underlie patient variation. A gene list ordered by genome-wide significance showed enrichment for the 7q22 target region. Modification of the gene list by weighting each sample for percent of del(7q) cells to account for the mosaic nature of these tumors further enhanced the frequency of 7q22 genes. Pathway analysis revealed two of the 19 significant functional networks were associated with development and the most represented pathway was protein ubiquitination, which can influence tumor development by stabilizing oncoproteins and destabilizing tumor suppressor proteins. Array CGH (aCGH) studies determined the only consistent genomic imbalance was deletion of 9.5 megabases from 7q22-7q31.1. Combining the aCGH data with the del(7q) UL mosaicism-weighted expression analysis resulted in a list of genes that are commonly deleted and whose copy number is correlated with significantly decreased expression. These genes include the proliferation inhibitor HPB1, the loss of expression of which has been associated with invasive breast cancer, as well as the mitosis integrity-maintenance tumor suppressor RINT1. This study provides a molecular signature of the del(7q) UL subgroup and will serve as a platform for future studies of tumor pathogenesis.

| S-EPMC2778251 | biostudies-literature

Expression data from normal myometrium, leiomyomata, and leiomyosarcomas

2015-01-08 | E-GEOD-64763 | biostudies-arrayexpress

Gene expression profiling of prostate cancer

Project description:To better understand the molecular mechanism that underlay tumorigenesis and progression of prostate cancer (PCa), we studied the gene expression profiles of sixteen PCa compared to their matched normal tissues. Using Significance Analysis of Microarrays, we identified 53 genes differentially expressed that were more than 2 fold up- or down-regulated in at least 50 % of the tumors. Keywords: disease state analysis

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