Limits...
Identification of prefoldin amplification (1q23.3-q24.1) in bladder cancer using comparative genomic hybridization (CGH) arrays of urinary DNA.

López V, González-Peramato P, Suela J, Serrano A, Algaba F, Cigudosa JC, Vidal A, Bellmunt J, Heredero O, Sánchez-Carbayo M - J Transl Med (2013)

Bottom Line: Supervised hierarchical clustering identified the gain at 1q23.3-q24.1 significantly correlated to stage (p = 0.011), and grade (p = 0.002).Moreover, PFND2 overexpression was significantly associated with poor disease-specific survival (p ≤0.0005).Genomic profiles of urinary DNA mirrowed bladder tumors.

View Article: PubMed Central - HTML - PubMed

Affiliation: Tumor Markers Group, Molecular Pathology Program, Spanish National Cancer Center, Melchor Fernandez Almagro 3, Madrid E-28029, Spain.

ABSTRACT

Background: Array-CGH represents a comprehensive tool to discover genomic disease alterations that could potentially be applied to body fluids. In this report, we aimed at applying array-CGH to urinary samples to characterize bladder cancer.

Methods: Urinary DNA from bladder cancer patients and controls were hybridized on 44K oligonucleotide arrays. Validation analyses of identified regions and candidates included fluorescent in situ hybridization (FISH) and immunohistochemistry in an independent set of bladder tumors spotted on custom-made tissue arrays (n = 181).

Results: Quality control of array-CGH provided high reproducibility in dilution experiments and when comparing reference pools. The most frequent genomic alterations (minimal recurrent regions) among bladder cancer urinary specimens included gains at 1q and 5p, and losses at 10p and 11p. Supervised hierarchical clustering identified the gain at 1q23.3-q24.1 significantly correlated to stage (p = 0.011), and grade (p = 0.002). The amplification and overexpression of Prefoldin (PFND2), a selected candidate mapping to 1q23.3-q24.1, correlated to increasing stage and tumor grade by means of custom-designed and optimized FISH (p = 0.013 and p = 0.023, respectively), and immunohistochemistry (p ≤0.0005 and p = 0.011, respectively), in an independent set of bladder tumors included in tissue arrays. Moreover, PFND2 overexpression was significantly associated with poor disease-specific survival (p ≤0.0005). PFND2 was amplified and overexpressed in bladder tumors belonging to patients providing urinary specimens where 1q23.3q24.1 amplification was detected by array-CGH.

Conclusions: Genomic profiles of urinary DNA mirrowed bladder tumors. Molecular profiling of urinary DNA using array-CGH contributed to further characterize genomic alterations involved in bladder cancer progression. PFND2 was identified as a tumor stratification and clinical outcome prognostic biomarker for bladder cancer patients.

Show MeSH

Related in: MedlinePlus

Array-CGH detected genomic imbalances in urinary specimens. A. Summary ideogram given by the CGH Analytics software for a representative urinary belonging to a patient with a pT1G2 bladder tumor (case 131HG). Average log2 ratio values along the chromosomes are represented by the red line. Displacement of the tracing of this red line to the right or left represents genomic gains or losses, respectively. The ideograms are ordered from chromosome 1 to 22, including chromosomes X and Y as well B. Detailed genomic DNA profile image for the same case obtained using the InSilicoArray CGH software. Average log10 ratio values of the CNVs along the chromosome are represented by the blue line. Displacement of the tracing of this blue line to the right or left represents genomic gains or losses, respectively. The profiles are ordered from chromosome 1 to 22, including chromosomes X and Y as well.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3750577&req=5

Figure 1: Array-CGH detected genomic imbalances in urinary specimens. A. Summary ideogram given by the CGH Analytics software for a representative urinary belonging to a patient with a pT1G2 bladder tumor (case 131HG). Average log2 ratio values along the chromosomes are represented by the red line. Displacement of the tracing of this red line to the right or left represents genomic gains or losses, respectively. The ideograms are ordered from chromosome 1 to 22, including chromosomes X and Y as well B. Detailed genomic DNA profile image for the same case obtained using the InSilicoArray CGH software. Average log10 ratio values of the CNVs along the chromosome are represented by the blue line. Displacement of the tracing of this blue line to the right or left represents genomic gains or losses, respectively. The profiles are ordered from chromosome 1 to 22, including chromosomes X and Y as well.

Mentions: The high-resolution genomic analysis for the urinary specimens belonging to bladder cancer patients was initially assessed using the CGH Analytics (Figure 1A), and the InSilicoArray CGH softwares (Figure 1B). Additional file 3: Figure S3 provides visualization for all of them.


Identification of prefoldin amplification (1q23.3-q24.1) in bladder cancer using comparative genomic hybridization (CGH) arrays of urinary DNA.

López V, González-Peramato P, Suela J, Serrano A, Algaba F, Cigudosa JC, Vidal A, Bellmunt J, Heredero O, Sánchez-Carbayo M - J Transl Med (2013)

Array-CGH detected genomic imbalances in urinary specimens. A. Summary ideogram given by the CGH Analytics software for a representative urinary belonging to a patient with a pT1G2 bladder tumor (case 131HG). Average log2 ratio values along the chromosomes are represented by the red line. Displacement of the tracing of this red line to the right or left represents genomic gains or losses, respectively. The ideograms are ordered from chromosome 1 to 22, including chromosomes X and Y as well B. Detailed genomic DNA profile image for the same case obtained using the InSilicoArray CGH software. Average log10 ratio values of the CNVs along the chromosome are represented by the blue line. Displacement of the tracing of this blue line to the right or left represents genomic gains or losses, respectively. The profiles are ordered from chromosome 1 to 22, including chromosomes X and Y as well.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750577&req=5

Figure 1: Array-CGH detected genomic imbalances in urinary specimens. A. Summary ideogram given by the CGH Analytics software for a representative urinary belonging to a patient with a pT1G2 bladder tumor (case 131HG). Average log2 ratio values along the chromosomes are represented by the red line. Displacement of the tracing of this red line to the right or left represents genomic gains or losses, respectively. The ideograms are ordered from chromosome 1 to 22, including chromosomes X and Y as well B. Detailed genomic DNA profile image for the same case obtained using the InSilicoArray CGH software. Average log10 ratio values of the CNVs along the chromosome are represented by the blue line. Displacement of the tracing of this blue line to the right or left represents genomic gains or losses, respectively. The profiles are ordered from chromosome 1 to 22, including chromosomes X and Y as well.
Mentions: The high-resolution genomic analysis for the urinary specimens belonging to bladder cancer patients was initially assessed using the CGH Analytics (Figure 1A), and the InSilicoArray CGH softwares (Figure 1B). Additional file 3: Figure S3 provides visualization for all of them.

Bottom Line: Supervised hierarchical clustering identified the gain at 1q23.3-q24.1 significantly correlated to stage (p = 0.011), and grade (p = 0.002).Moreover, PFND2 overexpression was significantly associated with poor disease-specific survival (p ≤0.0005).Genomic profiles of urinary DNA mirrowed bladder tumors.

View Article: PubMed Central - HTML - PubMed

Affiliation: Tumor Markers Group, Molecular Pathology Program, Spanish National Cancer Center, Melchor Fernandez Almagro 3, Madrid E-28029, Spain.

ABSTRACT

Background: Array-CGH represents a comprehensive tool to discover genomic disease alterations that could potentially be applied to body fluids. In this report, we aimed at applying array-CGH to urinary samples to characterize bladder cancer.

Methods: Urinary DNA from bladder cancer patients and controls were hybridized on 44K oligonucleotide arrays. Validation analyses of identified regions and candidates included fluorescent in situ hybridization (FISH) and immunohistochemistry in an independent set of bladder tumors spotted on custom-made tissue arrays (n = 181).

Results: Quality control of array-CGH provided high reproducibility in dilution experiments and when comparing reference pools. The most frequent genomic alterations (minimal recurrent regions) among bladder cancer urinary specimens included gains at 1q and 5p, and losses at 10p and 11p. Supervised hierarchical clustering identified the gain at 1q23.3-q24.1 significantly correlated to stage (p = 0.011), and grade (p = 0.002). The amplification and overexpression of Prefoldin (PFND2), a selected candidate mapping to 1q23.3-q24.1, correlated to increasing stage and tumor grade by means of custom-designed and optimized FISH (p = 0.013 and p = 0.023, respectively), and immunohistochemistry (p ≤0.0005 and p = 0.011, respectively), in an independent set of bladder tumors included in tissue arrays. Moreover, PFND2 overexpression was significantly associated with poor disease-specific survival (p ≤0.0005). PFND2 was amplified and overexpressed in bladder tumors belonging to patients providing urinary specimens where 1q23.3q24.1 amplification was detected by array-CGH.

Conclusions: Genomic profiles of urinary DNA mirrowed bladder tumors. Molecular profiling of urinary DNA using array-CGH contributed to further characterize genomic alterations involved in bladder cancer progression. PFND2 was identified as a tumor stratification and clinical outcome prognostic biomarker for bladder cancer patients.

Show MeSH
Related in: MedlinePlus