ABSTRACT: Integrated genomic and gene expression profiling identifies two major gene/genomic circuits operating in urothelial carcinoma (gene expression)
Project description:This SuperSeries is composed of the following subset Series: GSE32535: Integrated genomic and gene expression profiling identifies two major gene/genomic circuits operating in urothelial carcinoma (genomic) GSE32548: Integrated genomic and gene expression profiling identifies two major gene/genomic circuits operating in urothelial carcinoma (gene expression) Refer to individual Series
Project description:Genomic and gene expression profiling identifies two major gene/genomic circuits operating in urothelial carcinoma 131 primary bladder cancer tumor samples were analyzed on Illumina gene expression Bead Arrays.
Project description:Integrated genomic and gene expression profiling identifies two major gene/genomic circuits operating in urothelial carcinoma (genomic)
Project description:Genomic and gene expression profiling identifies two major gene/genomic circuits operating in urothelial carcinoma 146 primary bladder cancer tumor samples were analyzed on BAC array containing ~32 000 BAC clones. Arrays were produced at the Swegene Centre for Integrative Biology at Lund University (SCIBLU).
Project description:[original title] Combined gene expression and genomic profiling define two intrinsic molecular subtypes of urothelial carcinoma and gene signatures for molecular grading and outcome. In the present investigation we sought to refine the classification of urothelial carcinoma by combining information on gene expression, genomic, and gene mutation levels. For these purposes we performed gene expression analysis of 144 carcinomas, and whole genome array-CGH analysis and mutation analyses of FGFR3, PIK3CA, KRAS, HRAS, NRAS, TP53, CDKN2A, and TSC1, in 103 of these cases. Hierarchical cluster analysis identified two intrinsic molecular subtypes, MS1 and MS2, which were validated and defined by the same set of genes in three independent bladder cancer data sets. The two subtypes differed with respect to gene expression and mutation profiles, as well as with the level of genomic instability. The data shows that genomic instability was the most distinguishing genomic feature of MS2 tumors, and that this trait was not dependent on TP53/MDM2 alterations. By combining molecular and pathological data it was possible to distinguish two molecular subtypes of Ta and T1 tumors, respectively. In addition, we define gene signatures validated in two independent data sets that classify urothelial carcinoma into low (G1/G2) and high grade (G3) tumors as well as non-muscle and muscle-invasive tumors with high precisions and sensitivities, suggesting molecular grading as a relevant complement to standard pathological grading. We also present a gene expression signature with independent prognostic impact on metastasis and disease specific survival. We conclude that the combination of molecular and histopathological classification systems may provide a strong improvement for bladder cancer classification and produce new insights into the development of this tumor type.
Project description:Guisoni2016 - Cis-regulatory system (CRS) can
drive sustained oscillations
This model is described in the article:
Promoters Architecture-Based
Mechanism for Noise-Induced Oscillations in a Single-Gene
Circuit.
Guisoni N, Monteoliva D, Diambra
L.
PLoS ONE 2016; 11(3): e0151086
Abstract:
It is well known that single-gene circuits with negative
feedback loop can lead to oscillatory gene expression when they
operate with time delay. In order to generate these
oscillations many processes can contribute to properly timing
such delay. Here we show that the time delay coming from the
transitions between internal states of the cis-regulatory
system (CRS) can drive sustained oscillations in an
auto-repressive single-gene circuit operating in a small volume
like a cell. We found that the cooperative binding of repressor
molecules is not mandatory for a oscillatory behavior if there
are enough binding sites in the CRS. These oscillations depend
on an adequate balance between the CRS kinetic, and the
synthesis/degradation rates of repressor molecules. This
finding suggest that the multi-site CRS architecture can play a
key role for oscillatory behavior of gene expression. Finally,
our results can also help to synthetic biologists on the design
of the promoters architecture for new genetic oscillatory
circuits.
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Project description:Smoking is a major risk factor for Urothelial carcinoma (UC). However the complex mechanisms, how smoking promotes carcinogenesis and tumour progression, remain obscure. A microarray based approached was therefore performed to detect the smoking derived gene expression alteration in non-malignant and malignant urothelial tissues from patients with superficial or invasive UC. Smoking enhanced cell migration and response to tissue damages. In non-malignant tissues smoking induced immune response and altered the cytoskeleton. In urothelial carcinoma, smoking altered extracellular and chromosome structures. Smoking affected tissues from patients with invasive carcinomamore strongly, up-regulating particularly growth factors and oncogenes in non-malignant tissue of patients with invasive but not with superficial carcinoma. In former smokers, comparable changes were seen in tissues form patients with invasive disease while they were minor or reversed in tissue of patients with superficial disease. Best but not complete tissue repair was suggestedfor non-malignant tissue from patients with superficial tumours. we used microarray techniques to define gene expression profile which may explain the contribution of smoking to urothelial carcinoma. Gene expression profiling using GeneChip HG-U133A Plus 2.0 (Affymetrix) was performed on non-malignant and carcinogenic urothelium from six patients with superficial and six with invasive urothelial carcinoma, each group including two current, former, and non-smokers.
