Downregulation of DBC1 expression in acute lymphoblastic leukaemia is mediated by aberrant methylation of its promoter.
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.
San José-Enériz
Edurne
E
Foundation for Applied Medical Research, Division of Cancer and Area of Cell Therapy and Haematology Service, Clínica Universitaria, Universidad de Navarra, Pamplona, Spain.
Agirre
Xabier
X
Román-Gómez
José
J
Cordeu
Lucia
L
Garate
Leire
L
Jiménez-Velasco
Antonio
A
Vázquez
Iria
I
Calasanz
María José
MJ
Heiniger
Anabel
A
Torres
Antonio
A
Prósper
Felipe
F
D000293:Adolescent; D000328:Adult; D018797:Cell Cycle Proteins; D019175:DNA Methylation; D015536:Down-Regulation; D005260:Female; D017353:Gene Deletion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009419:Nerve Tissue Proteins; D016133:Polymerase Chain Reaction / Q000379:methods; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000097:blood* / Q000235:genetics
C112308:BRINP1 protein, human; D018797:Cell Cycle Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D025521:Tumor Suppressor Proteins