Methylation of tumour suppressor gene promoters in the presence and absence of transcriptional silencing in high hyperdiploid acute lymphoblastic leukaemia

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Methylation of tumour suppressor gene promoters in the presence and absence of transcriptional silencing in high hyperdiploid acute lymphoblastic leukaemia. / Paulsson, Kajsa; An, Qian; Moorman, Anthony V.; Parker, Helen; Molloy, Gael; Davies, Teresa; Griffiths, Mike; Ross, Fiona M.; Irving, Julie; Harrison, Christine J.; Young, Bryan D.; Strefford, Jon C.

In: British Journal of Haematology, Vol. 144, No. 6, 2009, p. 838-847.

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Paulsson, K, An, Q, Moorman, AV, Parker, H, Molloy, G, Davies, T, Griffiths, M, Ross, FM, Irving, J, Harrison, CJ, Young, BD & Strefford, JC 2009, 'Methylation of tumour suppressor gene promoters in the presence and absence of transcriptional silencing in high hyperdiploid acute lymphoblastic leukaemia', British Journal of Haematology, vol. 144, no. 6, pp. 838-847. https://doi.org/10.1111/j.1365-2141.2008.07523.x

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Paulsson, Kajsa ; An, Qian ; Moorman, Anthony V. ; Parker, Helen ; Molloy, Gael ; Davies, Teresa ; Griffiths, Mike ; Ross, Fiona M. ; Irving, Julie ; Harrison, Christine J. ; Young, Bryan D. ; Strefford, Jon C. / Methylation of tumour suppressor gene promoters in the presence and absence of transcriptional silencing in high hyperdiploid acute lymphoblastic leukaemia. In: British Journal of Haematology. 2009 ; Vol. 144, No. 6. pp. 838-847.

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TY - JOUR

T1 - Methylation of tumour suppressor gene promoters in the presence and absence of transcriptional silencing in high hyperdiploid acute lymphoblastic leukaemia

AU - Paulsson, Kajsa

AU - An, Qian

AU - Moorman, Anthony V.

AU - Parker, Helen

AU - Molloy, Gael

AU - Davies, Teresa

AU - Griffiths, Mike

AU - Ross, Fiona M.

AU - Irving, Julie

AU - Harrison, Christine J.

AU - Young, Bryan D.

AU - Strefford, Jon C.

PY - 2009

Y1 - 2009

N2 - Promoter methylation is a common phenomenon in tumours, including haematological malignancies. In the present study, we investigated 36 cases of high hyperdiploid (> 50 chromosomes) acute lymphoblastic leukaemia (ALL) with methylation-specific multiplex ligase-dependent probe amplification to determine the extent of aberrant methylation in this subgroup. The analysis, which comprised the promoters of 35 known tumour suppressor genes, showed that 16 genes displayed abnormal methylation in at least one case each. The highest number of methylated gene promoters seen in a single case was thirteen, with all but one case displaying methylation for at least one gene. The most common targets were ESR1 (29/36 cases; 81%), CADM1 (IGSF4, TSLC1; 25/36 cases; 69%), FHIT (24/36 cases; 67%) and RARB (22/36 cases; 61%). Interestingly, quantitative reverse transcription-polymerase chain reaction showed that although methylation of the CADM1 and RARB promoters resulted in the expected pattern of downregulation of the respective genes, no difference could be detected in FHIT expression between methylation-positive and -negative cases. Furthermore, TIMP3 was not expressed regardless of methylation status, showing that aberrant methylation does not always lead to gene expression changes. Taken together, our findings suggest that aberrant methylation of tumour suppressor gene promoters is a common phenomenon in high hyperdiploid ALL.

AB - Promoter methylation is a common phenomenon in tumours, including haematological malignancies. In the present study, we investigated 36 cases of high hyperdiploid (> 50 chromosomes) acute lymphoblastic leukaemia (ALL) with methylation-specific multiplex ligase-dependent probe amplification to determine the extent of aberrant methylation in this subgroup. The analysis, which comprised the promoters of 35 known tumour suppressor genes, showed that 16 genes displayed abnormal methylation in at least one case each. The highest number of methylated gene promoters seen in a single case was thirteen, with all but one case displaying methylation for at least one gene. The most common targets were ESR1 (29/36 cases; 81%), CADM1 (IGSF4, TSLC1; 25/36 cases; 69%), FHIT (24/36 cases; 67%) and RARB (22/36 cases; 61%). Interestingly, quantitative reverse transcription-polymerase chain reaction showed that although methylation of the CADM1 and RARB promoters resulted in the expected pattern of downregulation of the respective genes, no difference could be detected in FHIT expression between methylation-positive and -negative cases. Furthermore, TIMP3 was not expressed regardless of methylation status, showing that aberrant methylation does not always lead to gene expression changes. Taken together, our findings suggest that aberrant methylation of tumour suppressor gene promoters is a common phenomenon in high hyperdiploid ALL.

KW - acute lymphoblastic leukaemia

KW - high hyperdiploid

KW - methylation

U2 - 10.1111/j.1365-2141.2008.07523.x

DO - 10.1111/j.1365-2141.2008.07523.x

M3 - Article

VL - 144

SP - 838

EP - 847

JO - British Journal of Haematology

T2 - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 6

ER -