Associations between chromosomal aberrations visualized by MDS.

<p>Recurrent FGAs, HDs, and MRDs, as well as recurrent large chromosome arm deletions were included in the analysis. FGAs and HDs present in <5% of samples were excluded. Aberrations with significant positive associations, as determined by hypergeometric tests, are indicated in red and connected with green lines. Aberrations located to the same chromosomes are circled in gray for visualization purposes.</p

Summary of patient material.

<p>Summary of patient material.</p

DNA copy number alterations in 146 bladder tumors.

<p><b>A</b>) Whole genome heatmap representing relative copy number profiles of the samples. Segments of gains or deletions are color-coded according their relative log2 copy number ratios. <b>B</b>) DNA copy number frequency plot of gains (red) and losses (blue). Above: Recurrent high-level focal amplifications (FGA; red) are indicated by red bars and labeled according to their cytogenetic localization. Below: Recurrent homozygous deleted regions (HD; blue) and recurrent minimal regions of deletions (MRD; green) labeled according to their respective cytogenetic localization.</p

Integrated analysis of genomic alterations, gene mutations, and gene expression data.

<p><b>A</b>) Recurrent genomic alterations with significant association to gene expression subtypes. Activating mutation of <i>FGFR3</i>, <i>PIK3CA</i>, and <i>RAS</i>, and inactivating mutations of <i>CDKN2A</i>, as well as amplifications of <i>FGFR3</i> and <i>RAF1</i>, and TP53/MDM2 status is also displayed. Within each HCA group, samples are ordered according to their relative <i>FGFR3</i> expression. Dashed vertical lines, which define subsets within each HCA group, are drawn with respect to the E2F3, RB1, 5p, RAF1, and RAS alterations pattern and FGFR3 expression. Amplifications and homozygous deletions are indicated in black. Gains and deletions are indicated in gray. Activating/inactivating mutations are indicated in black. <b>B</b>) Heatmap representing relative expression levels of selected genes and the Bild E2F3 signature <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038863#pone.0038863-Bild1" target="_blank">[17]</a>. Green, low expression; red high expression. <b>C</b>) Frequencies of selected genomic alterations in gene expression subgroups.</p

Genomic networks and survival analysis of genomic subtypes.

<p><b>A</b>) MDS plot based on the subset of genomic alterations (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038863#pone-0038863-g004" target="_blank">Figure 4A</a>) and categorized gene expression data (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038863#pone.0038863.s003" target="_blank">Figure S3B</a>) that showed at least one instance of significant positive or negative association in a pair-wise hypergeometric tests. Green lines, significant positive association; red lines, significant negative association. <b>B</b>) Kaplan-Meier analysis of tumors grouped according to a combination of gene expression and genomic alteration patterns using disease specific survival (DSS) as endpoint.</p

A) 1-Pearson correlation distances among 8 normal samples, metachronous samples from 7 patients, 62 unique Ta samples, and 19 unique T1 samples estimates from expression data obtained from the 25k cDNA platform

B) 1-Pearson correlation distances among 7 normal samples, meta- or synchronous tumors from 12 patients, and 36 unique T1 tumors estimated from expression data obtained from 36k oligonucleotide platform. The calculation of distances among meta- and synchronous is based on distances among tumors originating from the same patients.<p><b>Copyright information:</b></p><p>Taken from "Recurrent and multiple bladder tumors show conserved expression profiles"</p><p>http://www.biomedcentral.com/1471-2407/8/183</p><p>BMC Cancer 2008;8():183-183.</p><p>Published online 30 Jun 2008</p><p>PMCID:PMC2483988.</p><p></p

Validation of gene expression data by IHC on tissue microarray.

<p><b>A</b>) Barplots summarizing tumor cell protein scores of selected proteins in tumors stratified according to the gene expression subtypes. Error bars represent ±SEM. <b>B</b>) IHC stainings of two representative HC1 (top) and HC5 samples (bottom).</p

Genomic complexity is associated with UC gene expression subtypes.

<p><b>A</b>) Hierarchical cluster analysis (HCA) on gene expression data segregated the tumors into five clusters, HC1 to HC5. Samples within each HCA group are ordered according to their relative FGFR3 expression (high expression left, low expression right). For each individual tumor, molecular signature (MS) type, pathological grade, stage, nFGA, fBAC, and TP53/MDM2 status is indicated. The relative expression levels for genes within the CIN signature are indicated by a heatmap below (green, low expression; red high expression). <b>B</b>) Boxplot illustrating the number of FGAs (nFGA) and frequency of genomic imbalances (fBAC) for samples within each HCA group. <b>C</b>) Boxplot of nFGA (left) and fBAC (right) for tumor samples when grouped on TP53/MDM2 status and MS type. P-values obtained by Wilcoxon statistics. n.s., not significant. <b>D</b>) Boxplot illustrating increased CIN score for samples with increased nFGAs (left) and fBAC (right). P-values obtained by ANOVA. <b>E</b> and <b>F</b>) Disease specific survival (DSS) analysis with tumors grouped according to nFGAs (0 vs ≥1 FGA) and CIN pathway score (above or below median), respectively.</p

A) HCA of 15 metachronous tumors from 7 patients, 84 unique tumors, and 8 normal samples hybridized to the 25k cDNA array

B) HCA of 38 meta- or synchronous tumors from 17 patients, 91 unique tumors, and 7 normal samples hybridized to the 36k oligonucleotide array. Meta- and synchronous tumors from the same patients are colored the same.<p><b>Copyright information:</b></p><p>Taken from "Recurrent and multiple bladder tumors show conserved expression profiles"</p><p>http://www.biomedcentral.com/1471-2407/8/183</p><p>BMC Cancer 2008;8():183-183.</p><p>Published online 30 Jun 2008</p><p>PMCID:PMC2483988.</p><p></p

Kaplan-Meier estimates of overall survival and survival for causes other than bladder cancer for the cohort of non-muscle invasive bladder cancer (NMIBC) patients and their matched comparison cohort.

Kaplan-Meier estimates of overall survival and survival for causes other than bladder cancer for the cohort of non-muscle invasive bladder cancer (NMIBC) patients and their matched comparison cohort.</p