A Genome-wide screen identifies frequently methylated genes in haematological and epithelial cancers

Molecular Cancer

Research

Gerd P Pfeifer¹  Tibor A Rauch¹  Richard E Clark²  Lihui Wang²  Eamonn R Maher³  Farida Latif³  Thomas Dunwell³  Dean Gentle³  Ashraf Dallol³  Luke Hesson³  Daniel Catchpoole⁴ 

[1] Beckman Research Institute, City of Hope, 1500 E. Duarte Road, 91010, Duarte, CA, USA;Department of Haematology, Royal Liverpool University Hospital, L7 8XP, Liverpool, UK;Department of Medical and Molecular Genetics, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, B15 2TT, Birmingham, UK;The Children's Hospital at Westmead, Locked Bag 4001, 2145, Westmead, NSW, Australia;

关键词: Acute Lymphoblastic Leukemia;    Chronic Myeloid Leukemia;    Leukemia Cell Line;    Chronic Myeloid Leukemia Patient;    Blast Crisis;   

DOI  :  10.1186/1476-4598-9-44

 received in 2009-11-18, accepted in 2010-02-25,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundGenetic 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.ResultsHere 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 T-ALL. 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.ConclusionIn 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.

【 授权许可】

Unknown   
© Dunwell et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.