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Integrated genomic and gene expression profiling identifies two major gene/genomic circuits operating in urothelial carcinoma

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE32549 | GEO | 2012/06/18

SECONDARY ACCESSION(S): PRJNA147013

REPOSITORIES: GEO

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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

2012-06-18 | GSE32535 | GEO

Integrated genomic and gene expression profiling identifies two major gene/genomic circuits operating in urothelial carcinoma

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

2012-06-17 | E-GEOD-32549 | biostudies-arrayexpress

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).

2012-06-17 | E-GEOD-32535 | biostudies-arrayexpress

Integrated genomic and gene expression profiling identifies two major gene/genomic circuits operating in urothelial carcinoma (gene expression)

Project description:Genomic and gene expression profiling identifies two major gene/genomic circuits operating in urothelial carcinoma

2012-06-18 | GSE32548 | GEO

Integrated genomic and gene expression profiling identifies two major genomic circuits in urothelial carcinoma.

Project description:Similar to other malignancies, urothelial carcinoma (UC) is characterized by specific recurrent chromosomal aberrations and gene mutations. However, the interconnection between specific genomic alterations, and how patterns of chromosomal alterations adhere to different molecular subgroups of UC, is less clear. We applied tiling resolution array CGH to 146 cases of UC and identified a number of regions harboring recurrent focal genomic amplifications and deletions. Several potential oncogenes were included in the amplified regions, including known oncogenes like E2F3, CCND1, and CCNE1, as well as new candidate genes, such as SETDB1 (1q21), and BCL2L1 (20q11). We next combined genome profiling with global gene expression, gene mutation, and protein expression data and identified two major genomic circuits operating in urothelial carcinoma. The first circuit was characterized by FGFR3 alterations, overexpression of CCND1, and 9q and CDKN2A deletions. The second circuit was defined by E3F3 amplifications and RB1 deletions, as well as gains of 5p, deletions at PTEN and 2q36, 16q, 20q, and elevated CDKN2A levels. TP53/MDM2 alterations were common for advanced tumors within the two circuits. Our data also suggest a possible RAS/RAF circuit. The tumors with worst prognosis showed a gene expression profile that indicated a keratinized phenotype. Taken together, our integrative approach revealed at least two separate networks of genomic alterations linked to the molecular diversity seen in UC, and that these circuits may reflect distinct pathways of tumor development.

| S-EPMC3369837 | biostudies-literature

Integrated genomic and gene expression profiling identifies two major gene/genomic circuits operating in urothelial carcinoma (gene expression)

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.

2012-06-17 | E-GEOD-32548 | biostudies-arrayexpress

Integrated genomic and gene expression profiling identifies two major gene/genomic circuits operating in urothelial carcinoma

Project description:Integrated genomic and gene expression profiling identifies two major gene/genomic circuits operating in urothelial carcinoma

| PRJNA147013 | ENA

Novel tumor subgroups of urothelial carcinoma of the bladder defined by integrated genomic analysis.

Project description:PurposeThere is a need for improved subclassification of urothelial carcinoma (UC) at diagnosis. A major aim of this study was to search for novel genomic subgroups.Experimental designWe assessed 160 tumors for genome-wide copy number alterations and mutation in genes implicated in UC. These comprised all tumor grades and stages and included 49 high-grade stage T1 (T1G3) tumors.ResultsOur findings point to the existence of genomic subclasses of the "gold-standard" grade/stage groups. The T1G3 tumors separated into 3 major subgroups that differed with respect to the type and number of copy number events and to FGFR3 and TP53 mutation status. We also identified novel regions of copy number alteration, uncovered relationships between molecular events, and elucidated relationships between molecular events and clinico-pathologic features. FGFR3 mutant tumors were more chromosomally stable than their wild-type counterparts and a mutually exclusive relationship between FGFR3 mutation and overrepresentation of 8q was observed in non-muscle-invasive tumors. In muscle-invasive (MI) tumors, metastasis was positively associated with losses of regions on 10q (including PTEN), 16q and 22q, and gains on 10p, 11q, 12p, 19p, and 19q. Concomitant copy number alterations positively associated with TP53 mutation in MI tumors were losses on 16p, 2q, 4q, 11p, 10q, 13q, 14q, 16q, and 19p, and gains on 1p, 8q, 10q, and 12q. Significant complexity was revealed in events affecting chromosome 9.ConclusionsThese findings may lead to improved biologic understanding and the development of prognostic biomarkers. Novel regions of copy number alteration may reveal potential therapeutic targets.

| S-EPMC5081094 | biostudies-literature

Urinary comprehensive genomic profiling predicts urothelial carcinoma recurrence and identifies responders to intravesical therapy.

Project description:Intravesical therapy (IVT) is the standard of care to decrease risk of recurrence and progression for high-grade nonmuscle-invasive bladder cancer. However, post-IVT recurrence remains common and the ability to risk-stratify patients before or after IVT is limited. In this prospectively designed and accrued cohort study, we examine the utility of urinary comprehensive genomic profiling (uCGP) for predicting recurrence risk following transurethral resection of bladder tumor (TURBT) and evaluating longitudinal IVT response. Urine was collected before and after IVT instillation and uCGP testing was done using the UroAmp™ platform. Baseline uCGP following TURBT identified patients with high (61%) and low (39%) recurrence risk. At 24 months, recurrence-free survival (RFS) was 100% for low-risk and 45% for high-risk patients with a hazard ratio (HR) of 9.3. Longitudinal uCGP classified patients as minimal residual disease (MRD) Negative, IVT Responder, or IVT Refractory with 24-month RFS of 100%, 50%, and 32%, respectively. Compared with MRD Negative patients, IVT Refractory patients had a HR of 10.5. Collectively, uCGP enables noninvasive risk assessment of patients following TURBT and induction IVT. uCGP could inform surveillance cystoscopy schedules and identify high-risk patients in need of additional therapy.

| S-EPMC10850796 | biostudies-literature

Integrated genomic analysis identifies clinically relevant subtypes of renal clear cell carcinoma.

Project description:BackgroundRenal cell carcinoma (RCC) account for over 80% of renal malignancies. The most common type of RCC can be classified into three subtypes including clear cell, papillary and chromophobe. ccRCC (the Clear Cell Renal Cell Carcinoma) is the most frequent form and shows variations in genetics and behavior. To improve accuracy and personalized care and increase the cure rate of cancer, molecular typing for individuals is necessary.MethodsWe adopted the genome, transcriptome and methylation HMK450 data of ccRCC in The Cancer Genome Atlas Network in this research. Consensus Clustering algorithm was used to cluster the expression data and three subtypes were found. To further validate our results, we analyzed an independent data set and arrived at a consistent conclusion. Next, we characterized the subtype by unifying genomic and clinical dimensions of ccRCC molecular stratification. We also implemented GSEA between the malignant subtype and the other subtypes to explore latent pathway varieties and WGCNA to discover intratumoral gene interaction network. Moreover, the epigenetic state changes between subgroups on methylation data are discovered and Kaplan-Meier survival analysis was performed to delve the relation between specific genes and prognosis.ResultsWe found a subtype of poor prognosis in clear cell renal cell carcinoma, which is abnormally upregulated in focal adhesions and cytoskeleton related pathways, and the expression of core genes in the pathways are negatively correlated with patient outcomes.ConclusionsOur work of classification schema could provide an applicable framework of molecular typing to ccRCC patients which has implications to influence treatment decisions, judge biological mechanisms involved in ccRCC tumor progression, and potential future drug discovery.

| S-EPMC5851245 | biostudies-literature

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