Present address: Department of Clinical Genetics, Lund University Hospital, Lund, Sweden.
Methylation of tumour suppressor gene promoters in the presence and absence of transcriptional silencing in high hyperdiploid acute lymphoblastic leukaemia
Article first published online: 22 DEC 2008
© 2008 The Authors. Journal Compilation © 2008 Blackwell Publishing Ltd
British Journal of Haematology
Volume 144, Issue 6, pages 838–847, March 2009
How to Cite
Paulsson, K., An, Q., Moorman, A. V., Parker, H., Molloy, G., Davies, T., Griffiths, M., Ross, F. M., Irving, J., Harrison, C. J., Young, B. D. and Strefford, J. C. (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, 144: 838–847. doi: 10.1111/j.1365-2141.2008.07523.x
- Issue published online: 19 FEB 2009
- Article first published online: 22 DEC 2008
- Received 17 September 2008; accepted for publication 23 October 2008
- high hyperdiploid;
- acute lymphoblastic leukaemia
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.