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

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Author

  • Kajsa Paulsson
  • Qian An
  • Anthony V. Moorman
  • Helen Parker
  • Gael Molloy
  • Teresa Davies
  • Mike Griffiths
  • Fiona M. Ross
  • Julie Irving
  • Christine J. Harrison
  • Bryan D. Young
  • Jon C. Strefford
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Summary, in English

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.

Publishing year

2009

Language

English

Pages

838-847

Publication/Series

British Journal of Haematology

Volume

144

Issue

6

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Hematology

Keywords

  • acute lymphoblastic leukaemia
  • high hyperdiploid
  • methylation

Status

Published

ISBN/ISSN/Other

  • ISSN: 0007-1048