Project description:We identified an altered miRNA expression in adenocarcinoma of the uterine cervix compared with normal cervix and futhermore analyzed their association with clinicopthologic characteristics.
Project description:This SuperSeries is composed of the following subset Series: GSE30758: Epigenome analysis of normal cells from the uterine cervix in a nested prospective case control study within the ARTISTIC trial GSE30759: Epigenome analysis of normal and cancer tissue from the uterine cervix Refer to individual Series
Project description:We identified an altered miRNA expression in adenocarcinoma of the uterine cervix compared with normal cervix and futhermore analyzed their association with clinicopthologic characteristics. miRNA expression was measured in four cancerous tissues from the cervical adenocarcinoma and four non-cancerous from the normal uterine cerivx respectively, all of which were obtained from different donors.
Project description:Squamocolumnar junction (SCJ) of the uterine cervix is a target of human papilloma virus (HPV) infection and thereby a putative cell-of-origin for uterine cervical cancer. However at present, in vitro models that accurately phenocopy its homeostasis is lacking. In this study, we aimed at establishing organoids of SCJ cells and identifying its characteristics. Samples were collected from the uterine cervix of 4 cases who underwent hysterectomy at our department, and processed to initiate organoid culture. Organoids were obtained from 3 samples among them, and they were analyzed both histologically and by transcriptome analysis.
Project description:Uterine fibroids are benign myometrial smooth muscle tumors of unknown etiology that when symptomatic are the most common indication for hysterectomy in the USA. We conducted an integrated analysis of fibroids and adjacent normal myometria by whole exome sequencing, DNA methylation (Human Methylation EPIC) array, and RNA-sequencing. Unsupervised clustering by DNA methylation segregated normal myometria and fibroids, and further separated the fibroids into subtypes marked by MED12 mutation, HMGA2 activation (HMGA2hi) and HMGA1 activation (HMGA1hi). Upregulation of HMGA2 expression in HMGA2hi fibroids did not always appear to be dependent on translocation, as has been historically described, and was associated with hypomethylation in the HMGA2 gene body. Furthermore, we found that expression of HOXA13 was highly upregulated in fibroids and that overexpression of HOXA13 in a myometrial cell line induced expression of genes classically associated with uterine fibroids. Transcriptome analyses of the most differentially expressed genes between cervix and myometrium also showed that uterine fibroids and normal cervix clustered together and apart from normal myometria. Together, our integrated analysis shows a role for epigenetic modification in fibroid biology and strongly suggests that homeotic transformation of myometrium cells to a more cervical phenotype is important for the etiology of the disease.
Project description:Uterine fibroids are benign myometrial smooth muscle tumors of unknown etiology that when symptomatic are the most common indication for hysterectomy in the USA. We conducted an integrated analysis of fibroids and adjacent normal myometria by whole exome sequencing, DNA methylation (Human Methylation EPIC) array, and RNA-sequencing. Unsupervised clustering by DNA methylation segregated normal myometria and fibroids, and further separated the fibroids into subtypes marked by MED12 mutation, HMGA2 activation (HMGA2hi) and HMGA1 activation (HMGA1hi). Upregulation of HMGA2 expression in HMGA2hi fibroids did not always appear to be dependent on translocation, as has been historically described, and was associated with hypomethylation in the HMGA2 gene body. Furthermore, we found that expression of HOXA13 was highly upregulated in fibroids and that overexpression of HOXA13 in a myometrial cell line induced expression of genes classically associated with uterine fibroids. Transcriptome analyses of the most differentially expressed genes between cervix and myometrium also showed that uterine fibroids and normal cervix clustered together and apart from normal myometria. Together, our integrated analysis shows a role for epigenetic modification in fibroid biology and strongly suggests that homeotic transformation of myometrium cells to a more cervical phenotype is important for the etiology of the disease.
Project description:Small cell neuroendocrine carcinoma (SCNEC) of the uterine cervix is a rare disease with a poor prognosis. The lack of established disease models has hampered therapy development. We established a panel of organoid from patients of SCNEC of the uterine cervix. Sensitivity assays against clinically used drugs revealed remarkable variations between the lines, and we successfully identified specific gene sets which likely contribute to the sensitivity to the tested drugs. Of note, we found one line which was exceptionally sensitive to irinotecan, and investigated the mode of action in the case. Chemotherapeutic drug sensitivity assays using SCNEC CTOS lines obtained from primary patient samples with a high success rate may provide useful information for treating SCNEC.
Project description:Oncogenic human papillomaviruses (HPVs) are associated with nearly all carcinomas of the uterine cervix and have also become an increasingly important factor in the etiology of a subset of oropharyngeal tumors. HPV-associated head and neck cancers (HNSCCs) have a distinct risk profile and appreciate a prognostic advantage compared to HPV-negative HNSCC. We analyzed the genome-wide expression patterns in two HPV(+) and two HPV(-) squamous cell carcinoma (SCC) cell lines.
Project description:Thiele2013 - Cervix uterine glandular cells
The model of cervix uterine glandular cells metabolism is derived from the community-driven global reconstruction of human metabolism (version 2.02, MODEL1109130000
).
This model is described in the article:
A community-driven global reconstruction of human metabolism.
Thiele I, et al
.
Nature Biotechnology
Abstract:
Multiple models of human metabolism have been reconstructed, but each represents only a subset of our knowledge. Here we describe Recon 2, a community-driven,
consensus 'metabolic reconstruction', which is the most comprehensive representation of human metabolism that is applicable to computational modeling. Compared
with its predecessors, the reconstruction has improved topological and functional features, including ~2x more reactions and ~1.7x more unique metabolites. Using
Recon 2 we predicted changes in metabolite biomarkers for 49 inborn errors of metabolism with 77% accuracy when compared to experimental data. Mapping metabolomic
data and drug information onto Recon 2 demonstrates its potential for integrating and analyzing diverse data types. Using protein expression data, we automatically
generated a compendium of 65 cell type-specific models, providing a basis for manual curation or investigation of cell-specific metabolic properties. Recon 2 will
facilitate many future biomedical studies and is freely available at http://humanmetabolism.org/.
This model is hosted on BioModels Database
and identified by: MODEL1310110026
.
To cite BioModels Database, please use: BioModels Database: An enhanced,
curated and annotated resource for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer
to CC0 Public Domain Dedication
for more information.