CpG Island microarray probe sequences derived from a physical library are representative of CpG Islands annotated on the human genome

Heisler, Lawrence E.; Torti, Dax; Boutros, Paul C.; Watson, John D.; Chan, Chung-hong; Winegarden, Neil; Takahashi, Mark; Yau, Patrick; Huang, Tim Hui-Ming; Farnham, Peggy J.; Jurišica, Igor; Woodgett, James R.; Bremner, Rod; Penn, Linda Z.; Der, Sandy D.

doi:10.1093/nar/gki582

Cited by 87 publications

(76 citation statements)

References 37 publications

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“…A panel of 12 288 CpG island clones was created from the CGI genomic library from Cross et al, 1994, as part of the Human Genome Mapping Project Resource Center (Heisler et al, 2005). Inserts from this CGI library were polymerase chain reaction (PCR)-amplified, purified by ethanol precipitation and then arrayed onto glass microscope slides by a specialised robot designed and created at Albert Einstein College of Medicine (Cheung et al, 1999;Adrien et al, 2006).…”

Section: Cpg Island Arraysmentioning

confidence: 99%

Identification of DNA hypermethylation of SOX9 in association with bladder cancer progression using CpG microarrays

et al. 2007

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CpG island arrays represent a high-throughput epigenomic discovery platform to identify global disease-specific promoter hypermethylation candidates along bladder cancer progression. DNA obtained from 10 pairs of invasive bladder tumours were profiled vs their respective normal urothelium using differential methylation hybridisation on custom-made CpG arrays (n ¼ 12 288 clones). Promoter hypermethylation of 84 clones was simultaneously shown in at least 70% of the tumours. SOX9 was selected for further validation by bisulphite genomic sequencing and methylation-specific polymerase chain reaction in bladder cancer cells (n ¼ 11) and primary bladder tumours (n ¼ 101). Hypermethylation was observed in bladder cancer cells and associated with lack of gene expression, being restored in vitro by a demethylating agent. In primary bladder tumours, SOX9 hypermethylation was present in 56.4% of the cases. Moreover, SOX9 hypermethylation was significantly associated with tumour grade and overall survival. Thus, this high-throughput epigenomic strategy has served to identify novel hypermethylated candidates in bladder cancer. In vitro analyses supported the role of methylation in silencing SOX9 gene. The association of SOX9 hypermethylation with tumour progression and clinical outcome suggests its relevant clinical implications at stratifying patients affected with bladder cancer.

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Section: Cpg Island Arraysmentioning

confidence: 99%

Identification of DNA hypermethylation of SOX9 in association with bladder cancer progression using CpG microarrays

et al. 2007

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“…32 This study demonstrates the value of the high-throughput CGI microarray 18 in cancer research. In a recent study 33 comparing this 9K library to another containing 12 192 (12K) clones, only 753 were found to be common between the two libraries, thus suggesting that the present study examined B50% of potential MseI-restricted CGI sequences in the human genome. Nevertheless, this does not diminish the value of finding many new, epigenetically altered genes that segregate with subclasses of NHL.…”

Section: Discussionmentioning

confidence: 88%

Differential DNA methylation patterns of small B-cell lymphoma subclasses with different clinical behavior

et al. 2006

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Non-Hodgkin's lymphoma (NHL) is a group of malignancies of the immune system with variable clinical behaviors and diverse molecular features. Despite the progress made in classification of NHLs based on classical methods, molecular classifications are a work in progress. Toward this goal, we used an arraybased technique called differential methylation hybridization (DMH) to study small B-cell lymphoma (SBCL) subtypes. A total of 43 genomic DMH experiments were performed. From these results, several statistical methods were used to generate a set of differentially methylated genes for further validation. Methylation of LHX2, POU3F3, HOXC10, NRP2, PRKCE, RAMP, MLLT2, NKX6.1, LRP1B and ARF4 was validated in cell lines and patient samples and demonstrated subtype-related preferential methylation patterns. For LHX2 and LRP1B, bisulfite sequencing, real-time reverse transcriptase-polymerase chain reaction and induction of gene expression following treatment with the demethylating agent, 5 0 -aza-2 0 -deoxycytidine, were confirmed. This new epigenetic information is helping to define molecular portraits of distinct subtypes of SBCL that are not recognized by current classification systems and provides valuable potential insights into the biology of these tumors.

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“…Spots enriched for p53 binding by more than twofold were selected for further analysis (approximately 150 loci). Chromosomal loci corresponding to enriched spots were identified from the CpG Island Microarray Bioinformatics Database (28) and the University Health Network Human CpG Island Microarray Database (see Materials and Methods). Repetitive loci, duplicated sequences, and loci farther than 10 kb from identified genes were removed from the list.…”

Section: Resultsmentioning

confidence: 99%

Functional Analysis of p53 Binding under Differential Stresses

Krieg

Hammond

Giaccia

2006

Molecular and Cellular Biology

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Hypoxia and DNA damage stabilize the p53 protein, but the subsequent effect that each stress has on transcriptional regulation of known p53 target genes is variable. We have used chromatin immunoprecipitation followed by CpG island (CGI) microarray hybridization to identify promoters bound by p53 under both DNA-damaging and non-DNA-damaging conditions in HCT116 cells. Using gene-specific PCR analysis, we have verified an association with CGIs of the highest enrichment (>2.5-fold) (REV3L, XPMC2H, HNRPUL1, TOR1AIP1, glutathione peroxidase 1, and SCFD2), with CGIs of intermediate enrichment (>2.2-fold) (COX7A2L, SYVN1, and JAG2), and with CGIs of low enrichment (>2.0-fold) (MYC and PCNA). We found little difference in promoter binding when p53 is stabilized by these two distinctly different stresses. However, expression of these genes varies a great deal: while a few genes exhibit classical induction with adriamycin, the majority of the genes are unchanged or are mildly repressed by either hypoxia or adriamycin. Further analysis using p53 mutated in the core DNA binding domain revealed that the interaction of p53 with CGIs may be occurring through both sequence-dependent and -independent mechanisms. Taken together, these experiments describe the identification of novel p53 target genes and the subsequent discovery of distinctly different expression phenomena for p53 target genes under different stress scenarios.The tumor microenvironment is a major factor influencing tumor growth, metastatic potential, and response to chemotherapeutic drugs and radiation therapy (7). The hypoxia-inducible factor (HIF) family of transcription factors regulates the expression of key enzymes in anaerobic glycolysis and proangiogenic factors (i.e., vascular endothelial growth factor), aiding cells in adapting to a low-oxygen environment (15). Thus, a tumor adapts to hypoxia first by sustaining itself via anaerobic metabolism and then by stimulating angiogenesis to acquire more nutrients and oxygen. However, the resulting vasculature tends to have aberrant structures with irregular blood flow and leaky walls, paradoxically creating regions of transient hypoxia and reoxygenation (76). Reoxygenation after hypoxia causes DNA damage, exacerbating genomic instability (25). The porous structure of the tumor vasculature may also provide an escape route for metastasizing cells. Repeated cycles of hypoxia, vascular formation, and reoxygenation select for cells that are more likely to survive in a restrictive environment. The consequences of this process are cancer cells that are more aggressive, more likely to metastasize, and more likely to be resistant to radiation and chemotherapy. Intimately tied to this process is the selection for cells that have lost the expression of functional p53 (19).A variety of cellular stresses, including DNA damage, oncogenic transformation, and hypoxia, stabilize the p53 protein by activating a host of stress-inducible kinases that phosphorylate p53 and MDM2, resulting in increased levels of p53 (17). Stabilized ...

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CpG Island microarray probe sequences derived from a physical library are representative of CpG Islands annotated on the human genome

Cited by 87 publications

References 37 publications

Identification of DNA hypermethylation of SOX9 in association with bladder cancer progression using CpG microarrays

Identification of DNA hypermethylation of SOX9 in association with bladder cancer progression using CpG microarrays

Differential DNA methylation patterns of small B-cell lymphoma subclasses with different clinical behavior

Functional Analysis of p53 Binding under Differential Stresses

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