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Background  Aberrant promoter DNA methylation has been reported in childhood acute lymphoblastic leukaemia (ALL) and has the potential to contribute to its onset and outcome. However, few reports demonstrate consistent, prevalent and dense promoter methylation, associated with tumour-specific gene silencing. By screening candidate genes, we have detected frequent and dense methylation of the  TESTIN  ( TES ) promoter.    Results  Bisulfite sequencing showed that 100% of the ALL samples (n = 20) were methylated at the  TES  promoter, whereas the matched remission (n = 5), normal bone marrow (n = 6) and normal PBL (n = 5) samples were unmethylated. Expression of  TES  in hyperdiploid, TEL-AML + , BCR-ABL + , and E2A-PBX +  subtypes of B lineage ALL was markedly reduced compared to that in normal bone marrow progenitor cells and in B cells. In addition  TES  methylation and silencing was demonstrated in nine out of ten independent B ALL propagated as xenografts in NOD/SCID mice.    Conclusion  In total, 93% of B ALL samples (93 of 100) demonstrated methylation with silencing or reduced expression of the  TES  gene. Thus,  TES  is the most frequently methylated and silenced gene yet reported in ALL.  TES , a LIM domain-containing tumour suppressor gene and component of the focal adhesion complex, is involved in adhesion, motility, cell-to-cell interactions and cell signalling. Our data implicate  TES  methylation in ALL and provide additional evidence for the involvement of LIM domain proteins in leukaemogenesis.

Silencing of TESTIN by dense biallelic promoter methylation is the most common molecular event in childhood acute lymphoblastic leukaemia