Genome-wide screening for genetic changes in a matched pair of benign and prostate cancer cell lines using array CGH

Brookman-Amissah, Nicola; Duchesnes, Cécile E.; Williamson, Magali; Wang, Q; Ahmed, Aamir; Feneley, Mark; Mackay, Alan; Freeman, Alex; Fenwick, Kerry; Iravani, Marjan; Weber, Barbara; Ashworth, Alan; Masters, J. R. W.

doi:10.1038/sj.pcan.4500826

Cited by 15 publications

(10 citation statements)

References 25 publications

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“…Increased expression (of about 25%) of the 20q genes was observed at passage 93 (Figure S5). These data, together with the high frequency of 20q amplification found in several cell lines [47], [48] and cancers support our assumption that amplification of 20q is a key factor in increasing cell proliferation rate.…”

Section: Resultssupporting

confidence: 87%

Amplification of the 20q Chromosomal Arm Occurs Early in Tumorigenic Transformation and May Initiate Cancer

et al. 2011

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Duplication of chromosomal arm 20q occurs in prostate, cervical, colon, gastric, bladder, melanoma, pancreas and breast cancer, suggesting that 20q amplification may play a causal role in tumorigenesis. According to an alternative view, chromosomal imbalance is mainly a common side effect of cancer progression. To test whether a specific genomic aberration might serve as a cancer initiating event, we established an in vitro system that models the evolutionary process of early stages of prostate tumor formation; normal prostate cells were immortalized by the over-expression of human telomerase catalytic subunit hTERT, and cultured for 650 days till several transformation hallmarks were observed. Gene expression patterns were measured and chromosomal aberrations were monitored by spectral karyotype analysis at different times. Several chromosomal aberrations, in particular duplication of chromosomal arm 20q, occurred early in the process and were fixed in the cell populations, while other aberrations became extinct shortly after their appearance. A wide range of bioinformatic tools, applied to our data and to data from several cancer databases, revealed that spontaneous 20q amplification can promote cancer initiation. Our computational model suggests that 20q amplification induced deregulation of several specific cancer-related pathways including the MAPK pathway, the p53 pathway and Polycomb group factors. In addition, activation of Myc, AML, B-Catenin and the ETS family transcription factors was identified as an important step in cancer development driven by 20q amplification. Finally we identified 13 "cancer initiating genes", located on 20q13, which were significantly over-expressed in many tumors, with expression levels correlated with tumor grade and outcome suggesting that these genes induce the malignant process upon 20q amplification.

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Section: Resultssupporting

confidence: 87%

Amplification of the 20q Chromosomal Arm Occurs Early in Tumorigenic Transformation and May Initiate Cancer

et al. 2011

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“…Microduplication of 20q11 leading to increased E2F1 expression has been reported in colon (48), esophagus (49), melanoma (50), and prostate tumors (51). To our knowledge this is the first reported association of a microduplication or microdeletion of E2F1 in non-cancer patients, emphasizing the range of actions of E2F1 in complex diseases, including infertility.…”

Section: Discussionmentioning

confidence: 99%

Genomic and genetic variation in E2F transcription factor-1 in men with nonobstructive azoospermia

Jorgez

Wilken

Addai

et al. 2015

Fertility and Sterility

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Objective To identify gene dosage changes associated with non-obstructive azoospermia (NOA) using array comparative genomic hybridization (aCGH). Design Prospective study. Patients 110 men with NOA and 78 fertile controls. Settings Medical School Interventions None Main Outcome Measure The study has four distinct analytic components: aCGH, a molecular karyotype that detects copy-number-variations (CNV), Taqman-CNV assays to validate CNVs, mutation identification by Sanger sequencing and histologic analyses of testicular tissues. Results A microduplication at 20q11.22 encompassing E2F1 was identified in one of eight men with NOA analyzed using aCGH. CNVs were confirmed and an additional 102 men with NOA screened using Taqman CNV assays for a total of 110 NOA men analyzed for CNVs in E2F1. Eight of 110 (7.3%) NOA men had microduplications or microdeletions of E2F1 that were absent in fertile controls. Conclusions E2F1 microduplications or microdeletions are present in NOA men (7.3%). Duplications or deletions of E2F1 occur very rarely in the general population (0.011%), but E2F1 gene dosage changes, previously reported only in cancers, are present in a subset of NOA men. These results recapitulate the infertility phenotype seen in mice lacking or over-expressing E2f1.

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“…These arrays consist of DNA from individual bacterial artificial chromosomes (BACs) tiled at varying intervals across the genome, where the resolution of the array is roughly proportional to the density of clones on the array. This technology has been used extensively over the past few years to study a wide variety of different cancer cell types (Brookman-Amissah et al, 2005;Nowak et al, 2005;Rossi et al, 2005;Varma et al, 2005). These aCGH studies, while more successful in identifying amplifications, have also been used to pinpoint consistent small deletions (Rossi et al, 2005).…”

Section: Introductionmentioning

confidence: 98%

Overlay analysis of the oligonucleotide array gene expression profiles and copy number abnormalities as determined by array comparative genomic hybridization in medulloblastomas

Lo¹,

Rossi²,

Burkhardt³

et al. 2006

Genes Chromosomes & Cancer

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Combined analysis of gene expression array data and array-based comparative genomic hybridization data have been used in a series of 26 pediatric brain tumors to define up- and downregulated genes that coincide with losses, gains, and amplifications involving specific chromosome regions. Frequent losses were defined in chromosome arms 3q, 6q, 8p, 10q, 16q, 17p, and gains were identified in chromosome 7, and chromosome arms 9p and 17q. Amplification of a 2p region was seen in only one tumor, which corresponded to increased expression of the MYCN and DDX1 genes. To facilitate the analysis of the two data sets, we have developed a custom overlay tool that defines genes that are underexpressed in regions of deletions and overexpressed in regions of gain, across the genome and specifically within regions showing recurrent involvement in medulloblastomas.

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Genome-wide screening for genetic changes in a matched pair of benign and prostate cancer cell lines using array CGH

Cited by 15 publications

References 25 publications

Amplification of the 20q Chromosomal Arm Occurs Early in Tumorigenic Transformation and May Initiate Cancer

Amplification of the 20q Chromosomal Arm Occurs Early in Tumorigenic Transformation and May Initiate Cancer

Genomic and genetic variation in E2F transcription factor-1 in men with nonobstructive azoospermia

Overlay analysis of the oligonucleotide array gene expression profiles and copy number abnormalities as determined by array comparative genomic hybridization in medulloblastomas

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