title: Aberrant hypomethylation of SALL4 gene in patients with myelodysplastic syndrome.
abstract: The abnormalities of SALL4 gene, which encodes a zinc-finger transcription factor and is essential for developmental events, have been found to be involved in tumorigenesis. In this study, we investigated the methylation status of the CpG island of SALL4 promoter region in myelodysplastic syndrome (MDS) using methylation-specific PCR (MSP). Aberrant hypomethylation of SALL4 gene was found in 21.7% (18/83) of the cases analyzed. A significantly positive correlation was identified between the level of SALL4 transcript and the status of SALL4 hypomethylation (R=0.641, P<0.001). No correlation was found between SALL4 hypomethylation and clinical parameters. However, the frequency of SALL4 hypomethylation significantly increased in higher risk MDS (14% in Low/Int-1 versus 39% in Int-2/High, P=0.031). The association between SALL4 hypomethylation and the mutations in three methylation modifiers (IDH1, IDH2 and DNMT3A) was not observed. Although the estimated 50% survival time of the SALL4-hypomethylated group was shorter than that of SALL4-methylated group (11.0 months vs. 20.0 months), the difference was not statistically significant (P=0.430). These findings suggest that hypomethylation of SALL4 promoter is a common event in MDS.
authors.affiliation: Laboratory Center, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu 212002, PR China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Lin
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
authors.forename: Dong-ming
authors.initials: DM
authors.lastname: Yao
authors.forename: Wei
authors.initials: W
authors.lastname: Qian
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: Cui-zhu
authors.initials: CZ
authors.lastname: Wang
authors.forename: Hai-yan
authors.initials: HY
authors.lastname: Chai
authors.forename: Ji-chun
authors.initials: JC
authors.lastname: Ma
authors.forename: Zhao-qun
authors.initials: ZQ
authors.lastname: Deng
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Qin
authors.initials: Q
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D005260:Female; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C000717967:DNMT3A protein, human; C472575:SALL4 protein, human; D014157:Transcription Factors; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A