%0 Journal Article %T Silencing of TESTIN by dense biallelic promoter methylation is the most common molecular event in childhood acute lymphoblastic leukaemia %A Robert J Weeks %A Ursula R Kees %A Sarah Song %A Ian M Morison %J Molecular Cancer %D 2010 %I BioMed Central %R 10.1186/1476-4598-9-163 %X 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.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.Methylation of gene promoters is a mechanism by which tumour suppressor genes can be inactivated. The role of promoter methylation in carcinogenesis has been convincingly demonstrated when gene methylation constitutes one of two events causing inactivation of well-documented tumour suppressor genes. Examples include, familial stomach cancer in which the non-mutated allele of CDH1 is silenced by promoter methylation [1] and sporadic renal cell cancer and retinoblastoma in which the non-deleted alleles of VHL and RB respectively are silenced [2,3].Distinction of genes whose methylation is causally associated with malignant transformation from those that are affected by non-specific methylation remains problematic. It is plausible that genes that are densely methylated in all cells within the leukaemic clone are more likely to be involved in tumourigenesis than those that are partially methylated in a low proportion of leukae %U http://www.molecular-cancer.com/content/9/1/163