Defining a 0.5-Mb Region of Genomic Gain on Chromosome 6p22 in Bladder Cancer by Quantitative-Multiplex Polymerase Chain Reaction

Abstract

Urothelial carcinomas, or transitional cell carcinomas, represent the vast majority of human bladder cancers. Early molecular events associated with superficial bladder cancers include losses on chromosome 9p/9q and mutations in the p53 and retinoblastoma tumor suppressor genes. 1,2 The genomic alterations associated with disease progression, defined as the evolution of superficial bladder tumors to higher pathological stages, are complex and poorly understood. Conventional metaphase-based comparative genomic hybridization (CGH) has been used by several groups of investigators to study copy number imbalances in bladder cancer specimens of all stages and grades. These studies have illustrated the genomic complexity of bladder cancer and have identified recurrent regions of DNA copy number increase or high level amplification on several chromosomes including; 1q, 5p, 6p, 8q, 10p, 12q, 17q, and 20q. 3-9 These genomic regions are thought to contain oncogenes that may be important in tumor progression.Metaphase CGH studies have demonstrated copy number gains or high level amplifications at 6p22 in 7 to 55% of urothelial carcinomas, involving primarily the bladder, 3-9 but also those arising in the renal pelvis. 10 In addition, Bruch et al 11 reported 6p22 gains in 6 of 8 bladder cancer cell lines. Recently, Veltman et al 12 confirmed the metaphase CGH findings using array-based CGH to show copy number gains at 6p22 in 11 of a series of 41 bladder tumors. The changes at 6p22 in bladder cancer have been associated with high tumor cell proliferative activity, 9 tumors of high histological grade that are predominantly invasive, 3-9 and patients with distant metastases at initial presentation. 8 Based on these findings,

Genomic gains on chromosome 1q in retinoblastoma: Consequences on gene expression and association with clinical manifestation

“…Possibly, gains in these samples were missed by CGH because the resolution of this technique, both spatial and quantitative, is inferior to that of QMPCR. 30,31 None of the tumors analyzed here showed high-level amplification of one or more specific markers on 1q32. This is also true for the results of QMPCR analysis of 1q21, a region that was included in QMPCR analysis because of the results of expression analysis after SAM.…”

“…In this respect, our results confirm previous reports. 30,31 We cannot exclude the possibility that some tumors identified as having gains by QMPCR may have no 1q gains. However, we controlled for stochastic and systematic errors, which are potential sources of false-positive results, by redundant measurements of some loci and by analysis of samples with known copy numbers of chromosome 1q, respectively.…”

KIF14 is a candidate oncogene in the 1q minimal region of genomic gain in multiple cancers

“…We then used QM-PCR of STSs to rapidly narrow regions of gain or loss in tumors: gain at 6p22 (Chen et al, 2002) and loss at 16q22 (Marchong et al, 2004) in retinoblastoma and gain at 6p22 in bladder cancer (Evans et al, 2004). This technique is a powerful method for high-resolution, region-specific examination of genomic changes in large numbers of tumor samples.…”

“…The selected markers were without known polymorphisms recorded in UniSTS, had sizes ranging from 175 to 316 bp, and did not lie within genomic duplicons (Bailey et al, 2001). The internal control STS was WI-7221 (335 bp) at 10q21, a genomic region that was not gained or lost in our CGH study of retinoblastoma (Chen et al, 2001), and which was used as a two-copy control in our previous genomic QM-PCR analyses (Chen et al, 2002;Evans et al, 2004;Marchong et al, 2004). This region is also rarely aberrant in breast cancer: 6.5% of 414 cases in the Progenetix database (Baudis and Cleary, 2001).…”

p300/CBP-associated Factor Drives DEK into Interchromatin Granule Clusters

“…DEK expression is also increased in multiple malignancies, including bladder cancer, hepatocellular carcinoma, glioblastoma, melanoma, T-cell large granular lymphocyte leukemia, and acute myeloid leukemia, independent of the t(6,9) chromosomal translocation (1,2,(7)(8)(9). Indeed, a gene profile analysis of 41 adult patients with acute myeloid leukemia using quantitative real-time PCR showed that DEK is overexpressed in 98% of the cases (10).…”