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

T Dunwell; L Hesson; TA Rauch; L Wang; RE Clark; Ashraf Dallol; Dean Gentle; D Catchpoole; Eamonn Maher; GP Pfeifer; Farida Latif

doi:10.1186/1476-4598-9-44

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

T Dunwell, L Hesson, TA Rauch, L Wang, RE Clark, Ashraf Dallol, Dean Gentle, D Catchpoole, Eamonn Maher, GP Pfeifer, Farida Latif

Birmingham Medical School

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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

Original language	English
Pages (from-to)	44
Number of pages	1
Journal	Molecular Cancer
Volume	9
DOIs	https://doi.org/10.1186/1476-4598-9-44
Publication status	Published - 1 Feb 2010

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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",

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T1 - A Genome-wide screen identifies frequently methylated genes in haematological and epithelial cancers

AU - Dunwell, T

AU - Hesson, L

AU - Rauch, TA

AU - Wang, L

AU - Clark, RE

AU - Dallol, Ashraf

AU - Gentle, Dean

AU - Catchpoole, D

AU - Maher, Eamonn

AU - Pfeifer, GP

AU - Latif, Farida

PY - 2010/2/1

Y1 - 2010/2/1

N2 - 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

AB - 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

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VL - 9

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JO - Molecular Cancer

JF - Molecular Cancer

ER -

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

Abstract

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