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Downregulation of DBC1 expression in acute lymphoblastic leukaemia is mediated by aberrant methylation of its promoter
Author(s) -
San JoséEnériz Edurne,
Agirre Xabier,
RománGómez José,
Cordeu Lucia,
Garate Leire,
JiménezVelasco Antonio,
Vázquez Iria,
Calasanz María José,
Heiniger Anabel,
Torres Antonio,
Prósper Felipe
Publication year - 2006
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2006.06131.x
Subject(s) - methylation , dna methylation , downregulation and upregulation , microbiology and biotechnology , cancer research , biology , allele , gene , promoter , gene expression , demethylation , regulation of gene expression , cell culture , genetics
Summary The DBC1 gene is a potential tumour suppressor gene that is commonly hypermethylated in epithelial cancers. We studied the role of promoter hypermethylation in the regulation of DBC1 in acute lymphoblastic leukaemia (ALL) cell lines and 170 ALL patients at diagnosis. Abnormal methylation of DBC1 was observed in all ALL cell lines and in 17% of ALL patients. Moreover, DBC1 methylation was associated with decreased DBC1 expression, while treatment of ALL cells with 5‐Aza‐2′‐deoxycytidine resulted in demethylation of the promoter and upregulation of DBC1 expression. Fluorescence in situ hybridisation identified the deletion of one allele of DBC1 in some ALL cell lines, which indicated that the lack of DBC1 expression was due to deletion of one allele and methylation of the other. In conclusion, these results demonstrate, for the first time, that the expression of DBC1 is downregulated in a percentage of patients with ALL due to the hypermethylation of its promoter and/or gene deletion.