title: Abnormal methylation of the sex-determining region Y-box 17 (SOX17) promoter predicts poor prognosis in myelodysplastic syndrome.
abstract: BACKGROUND
  The sex-determining region Y-box 17 (SOX17) is a member of the high mobility group (HMG) transcription factor family, which plays critical roles in the regulation of development and stem/precursor cell function. Recent evidence demonstrated that SOX17 acts as a tumor-suppressor gene, at least partly though repression of Wnt pathway activity.
  
  
  METHODS
  Here we report that SOX17 methylation was detected in THP-1 and SKM-I cell lines and SOX17 mRNA levels was up-regulated by 5-aza-dC. To clarify the role of SOXI7 in MDS, methylation-specific PCR (MSP) was employed to examine the methylation status of SOX17 in 164 adult de novo MDS patients and 6 normal samples.
  
  
  RESULTS
  We found that SOX17 methylation was presented in 58.5% (n = 96) of these patients and none of the normal samples. Methylation was correlated significantly with World Health Organization (WHO) subtypes and international prognostic scoring system (IPSS) risk group. Patients with advanced stages of WHO subtypes (69.6% vs. 44.4%, p = 0.001) and higher risk IPSS subgroups (69.8% vs. 48.8%, p = 0.010) exhibited a significantly higher frequency of SOX17 methylation. Though multivariate analysis indicated that SOX17 methylation status was not the independent factor that impacted overall survival (OS) (HR = 0.097), there were significant differences in marrow blast levels and the IPSS risk subgroups between patients with and without SOX17 methylation.
  
  
  CONCLUSIONS
  These findings suggest that the hypermethylation of SOX17 promoter may be one of the early events in the development of MDS and predicts poor prognosis.
authors.forename: Rong
authors.initials: R
authors.lastname: Fan
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Zhao
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: He
authors.forename: Zhen-Ping
authors.initials: ZP
authors.lastname: Peng
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Tao
authors.initials: T
authors.lastname: Han
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Wang
authors.forename: Guo-Wei
authors.initials: GW
authors.lastname: Lin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D016009:Chi-Square Distribution; D019175:DNA Methylation; D018450:Disease Progression; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D010641:Phenotype; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000378:metabolism; D012307:Risk Factors; D055760:SOXF Transcription Factors / Q000235:genetics*; D013997:Time Factors; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D012333:RNA, Messenger; C109188:SOX17 protein, human; D055760:SOXF Transcription Factors