Document Details

Document Type : Article In Journal 
Document Title :
A Genome-wide screen identifies frequently methylated genes in haematological and epithelial cancers
A Genome-wide screen identifies frequently methylated genes in haematological and epithelial cancers
 
Document Language : English 
Abstract : Background: Genetic as well as epigenetic alterations are a hallmark of both epithelial and haematological malignancies. High throughput screens are required to identify epigenetic markers that can be useful for diagnostic and prognostic purposes across malignancies. Results: Here we report for the first time the use of the MIRA assay (methylated CpG island recovery assay) in combination with genome-wide CpG island arrays to identify epigenetic molecular markers in childhood acute lymphoblastic leukemia (ALL) on a genome-wide scale. We identified 30 genes demonstrating methylation frequencies of ≥25% in childhood ALL, nine genes showed significantly different methylation frequencies in B vs TALL. For majority of the genes expression could be restored in methylated leukemia lines after treatment with 5- azaDC. Forty-four percent of the genes represent targets of the polycomb complex. In chronic myeloid leukemia (CML) two of the genes, (TFAP2A and EBF2), demonstrated increased methylation in blast crisis compared to chronic phase (P < 0.05). Furthermore hypermethylation of an autophagy related gene ATG16L2 was associated with poorer prognosis in terms of molecular response to Imatinib treatment. Lastly we demonstrated that ten of these genes were also frequently methylated in common epithelial cancers. Conclusion: In summary we have identified a large number of genes showing frequent methylation in childhood ALL, methylation status of two of these genes is associated with advanced disease in CML and methylation status of another gene is associated with prognosis. In addition a subset of these genes may act as epigenetic markers across hematological malignancies as well as common epithelial cancers. 
ISSN : 1476-4598 
Journal Name : Molecular Cancer 
Volume : 9 
Issue Number : 44 
Publishing Year : 1431 AH
2010 AD
 
Article Type : Article 
Added Date : Monday, April 26, 2010 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
فريدة لطيفLatif, Farida InvestigatorDoctoratef.latif@bham.ac.uk
أشرف دلولDallol, Ashraf ResearcherDoctorate 

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