Multilevel whole-genome analysis reveals candidate biomarkers in clear cell renal cell carcinoma.

Renal cell carcinoma (RCC) is the most common neoplasm of the kidney. We conducted an integrated analysis of copy number, gene expression (mRNA and miRNA), protein expression, and methylation changes in clear cell renal cell carcinoma (ccRCC). We used a stepwise approach to identify the most significant copy number aberrations (CNA) and identified regions of peak and broad copy number gain and loss, including peak gains (3q21, 5q32, 5q34-q35, 7p11, 7q21, 8q24, 11q13, and 12q14) and deletions (1p36, 2q34-q37, 3p25, 4q33-q35, 6q23-q27, and 9p21).

Adenoviral-mediated pHyde gene transfer and cisplatin additively inhibit human prostate cancer growth by enhancing apoptosis.

Background: A novel gene, rat pHyde, has been cloned by us recently. The rat pHyde was shown by the same group to have growth inhibitory effects on human prostate cancer through the induction of apoptosis.

Methods: In this report, a human homologue, hpHyde of the rat pHyde, was cloned by cDNA libraries screening.

Identification of PEG10 as a progression related biomarker for hepatocellular carcinoma.

Widespread DNA copy number alterations are well recognized in hepatocellular carcinoma (HCC), although the affected genes expression remained largely undefined. In this study, we performed genome-wide analysis on HCC to examine the relationship between gene copy number and corresponding transcriptional changes. To ensure analysis on a homogenous population of tumor cells, integrative analysis of array-based CGH and expression profilings was performed on 20 HCC cell lines using a 19,200-element cDNA microarray platform.

Positional expression profiling indicates candidate genes in deletion hotspots of hepatocellular carcinoma.

Molecular characterizations of hepatocellular carcinoma have indicated frequent allelic losses on chromosomes 4q, 8p, 16q and 17p, where the minimal deleted regions have been further defined on 4q12-q23, 4q31-q35, 8p21-p22, 16q12.1-q23.1 and 17p13.

The use of whole genome amplification to study chromosomal changes in prostate cancer: insights into genome-wide signature of preneoplasia associated with cancer progression.

Background: Prostate cancer (CaP) is a disease with multifactorial etiology that includes both genetic and environmental components. The knowledge of the genetic basis of CaP has increased over the past years, mainly in the pathways that underlie tumourigenesis, progression and drug resistance. The vast majority of cases of CaP are adenocarcinomas that likely develop through a pre-malignant lesion and high-grade prostatic intraepithelial neoplasia (HPIN).

Concordant copy number and transcriptional activity of genes mapping to derivative chromosomes 8 during cellular immortalization in vitro.

Deletion, rearrangement, or amplification of sequences mapping to chromosome 8 are frequently observed in human prostate and other tumors. However, it is not clear whether these events alter the transcriptional activity of the affected genes. To examine this question, we have utilized oligonucleotide microarray technology and compared the transcriptional patterns of normal human prostate tissues and five immortalized cell lines carrying either two normal chromosomes 8 or one normal and one derivative chromosome 8.

High-resolution mapping of genomic imbalance and identification of gene expression profiles associated with differential chemotherapy response in serous epithelial ovarian cancer.

Array comparative genomic hybridization (aCGH) and microarray expression profiling were used to subclassify DNA and RNA alterations associated with differential response to chemotherapy in ovarian cancer. Two to 4 Mb interval arrays were used to map genomic imbalances in 26 sporadic serous ovarian tumors. Cytobands 1p36, 1q42-44, 6p22.

Karyotypic imbalances and differential gene expressions in the acquired doxorubicin resistance of hepatocellular carcinoma cells.

Administration of doxorubicin has been shown to prolong survival of patients with hepatocellular carcinoma (HCC). However, treatment regimen is often complicated by the emergence of drug resistance. The goal of our study is to enhance our understanding on the genetic changes that confer cellular chemoresistance to doxorubicin.

Transcriptional profiling identifies gene expression changes associated with IFN-alpha tolerance in hepatitis C-related hepatocellular carcinoma cells.

Purpose: Treatment with IFN-alpha therapy has been shown to exhibit antitumor effects on patients with hepatocellular carcinoma (HCC). However, individual responses remained unpredictable because of the frequent presence of intrinsic or acquired IFN-alpha resistance. Hence, delineation of molecular targets implicated in the resistant pathway holds value in refining the therapeutic benefits of IFN-alpha.

An integrated mBAND and submegabase resolution tiling set (SMRT) CGH array analysis of focal amplification, microdeletions, and ladder structures consistent with breakage-fusion-bridge cycle events in osteosarcoma.

Osteosarcoma (OS) is characterized by chromosomal instability and high-copy-number gene amplification. The breakage-fusion-bridge (BFB) cycle is a well-established mechanism of genomic instability in tumors and in vitro models used to study the origins of complex chromosomal rearrangements and cancer genome amplification. However, until now, there have been no high-resolution cytogenetic or genomic array studies of BFB events in OS.

Transcriptional profiling on chromosome 19p indicated frequent downregulation of ACP5 expression in hepatocellular carcinoma.

Chromosomal rearrangements unraveled by spectral karyotyping (SKY) indicated frequent chromosome 19 translocations in hepatocellular carcinoma (HCC). In an effort to characterize the aberrant 19 rearrangements in HCC, we performed positional mapping by fluorescence in-situ hybridization (FISH) in 10 HCC cell lines. SKY analysis indicated structural rearrangements of chromosome 19 in 6 cell lines, 4 of which demonstrated recurring 19p translocations with different partner chromosomes.

Genetic alterations in doxorubicin-resistant hepatocellular carcinoma cells: a combined study of spectral karyotyping, positional expression profiling and candidate genes.

Despite a prolongation of patient survival, the overall response of doxorubicin (DX) treatment on patients with hepatocellular carcinoma (HCC) remains modest. This is largely attributed to the development of tumor drug resistance either at the onset or during the course of treatment. To investigate the genetic changes associated with DX chemo-resistance, we examined the cytotoxic effect of DX on a panel of 9 HCC cell lines (HepG2, Hep3B, PLC/PRF/5, and six in-house established, HKCI-1, 2, 3 and 4, C1 and C2).

Evolution of 8p loss in transformed human prostate epithelial cells.

Deletion or rearrangement of sequences that map to the short arm of chromosome 8 (8p) are frequently associated with human prostate tumorigenesis. These losses often involve the entire short arm of chromosome 8 or very large regions of distal or proximal 8p, and several putative tumor suppressor genes mapping to 8p have been described. However, the mechanism responsible for 8p loss during prostate tumorigenesis has not been elucidated.

Combined spectral karyotyping, multicolor banding, and microarray comparative genomic hybridization analysis provides a detailed characterization of complex structural chromosomal rearrangements associated with gene amplification in the osteosarcoma cell line MG-63.

The advancement of fluorescence in situ hybridization-based assays has permitted more refined delineation of chromosomal loci involved in complex chromosomal rearrangements (CCRs) and gene amplification. In this detailed molecular cytogenetic analysis, spectral karyotyping (SKY), multicolor banding (mBAND) analysis, and microarray comparative genomic hybridization (CGH) were used to refine the analysis of chromosomes with amplifications and small intrachromosomal rearrangements such as inverted duplications and interstitial deletions present in the osteosarcoma cell line MG-63. SKY analysis has limited resolving power to delineate cryptic chromosomal rearrangements, so mBAND assays were performed for a subset of chromosomes (i.

High-resolution mapping of amplifications and deletions in pediatric osteosarcoma by use of CGH analysis of cDNA microarrays.

Conventional cytogenetic and comparative genomic hybridization (CGH) studies have shown that osteosarcomas (OSs) are characterized by complex structural and numerical chromosomal alterations and gene amplification. In this study, we used high-resolution CGH to investigate recurrent patterns of genomic imbalance by use of DNA derived from nine OS tumors hybridized to a 19,200-clone cDNA microarray. In six OSs, there was copy number gain or amplification of 6p, with a minimal region of gain centering on segment 6p12.

Evidence of multifocality of telomere erosion in high-grade prostatic intraepithelial neoplasia (HPIN) and concurrent carcinoma.

Mechanisms underlying prostate cancer (CaP) initiation and progression are poorly understood. A chromosomal instability mechanism leading to the generation of numerical and structural chromosomal changes has been implicated in the preneoplastic and neoplastic stages of CaP. Telomere dysfunction is one potential mechanism associated with the onset of such instability.

Chromosomal localization of DNA amplifications in neuroblastoma tumors using cDNA microarray comparative genomic hybridization.

Conventional comparative genomic hybridization (CGH) profiling of neuroblastomas has identified many genomic aberrations, although the limited resolution has precluded a precise localization of sequences of interest within amplicons. To map high copy number genomic gains in clinically matched stage IV neuroblastomas, CGH analysis using a 19,200-feature cDNA microarray was used. A dedicated (freely available) algorithm was developed for rapid in silico determination of chromosomal localizations of microarray cDNA targets, and for generation of an ideogram-type profile of copy number changes.

Resolution of genotypic heterogeneity in prostate tumors using polymerase chain reaction and comparative genomic hybridization on microdissected carcinoma and prostatic intraepithelial neoplasia foci.

Prostate cancer (CaP) is a multifocal heterogenous disease. A major challenge in CaP research is to identify genetic biomarkers that herald aggressive transformation. To investigate the effect of tumor heterogeneity on the analysis of genomic aberration, we compared the results of comparative genomic hybridization (CGH) analysis of DNA extracted from tumor bulk against that of DNA amplified by degenerate oligonucleotide primed polymerase chain reaction (DOP-PCR) from homogeneous cell population obtained by laser capture microdissection of discrete tumor foci.

Parallel analysis of sporadic primary ovarian carcinomas by spectral karyotyping, comparative genomic hybridization, and expression microarrays.

Analysis of ovarian carcinomas has shown that karyotypes are often highly abnormal and cannot be identified with certainty by conventional cytogenetic methods. In this study, 17 tumors derived from 13 patients were analyzed by a combination of spectral karyotyping (SKY), comparative genomic hybridization (CGH), and expression microarrays. Within the study group, a total of 396 chromosomal rearrangements could be identified by SKY and CGH analysis.