title: CpG island methylation of tumor-related promoters occurs preferentially in undifferentiated carcinoma.
abstract: OBJECTIVE
  To understand the role of epigenetic inactivation of tumor-related genes in the pathogenesis of thyroid cancer, we investigated the methylation profile of distinct thyroid neoplasms.
  
  
  METHODS
  We analyzed the methylation pattern of 17 gene promoters in nine thyroid cancer cell lines and in 38 primary thyroid carcinomas (13 papillary thyroid carcinoma [PTC], 10 follicular thyroid carcinoma [FTC], 9 undifferentiated thyroid carcinoma [UTC], 6 medullary thyroid carcinoma [MTC]), 12 goiters, and 10 follicular adenomas (FA) by methylation- specific polymerase chain reaction (PCR). Epigenetic inactivation was validated by expression analysis.
  
  
  RESULTS
  Twelve of these genes (RASSF1A, p16(INK4A), TSHR, MGMT, DAPK, ERalpha, ERbeta, RARbeta, PTEN, CD26, SLC5A8, and UCHL1) were frequently methylated in UTC (15%-86%) and thyroid cancer cell lines (25%-100%). In the more aggressive UTC, the mean methylation index (MI = 0.44) was the highest compared to other thyroid alterations PTC (MI = 0.29, p = 0.123), FTC (MI = 0.15, p = 0.005), MTC (MI = 0.13; p = 0.017), FA (MI = 0.27; p = 0.075) and goiters (MI = 0.23; p = 0.024). Methylation of TSHR, MGMT, UCHL1, and p16 occurred preferentially in UTC and this inactivation was reverted by a demethylating agent.
  
  
  CONCLUSIONS
  Our results show that hypermethylation of several tumor-related gene promoters is a frequent event in UTC. The hypermethylation status may be reversed by DNA demethylating agents. Their clinical value remains to be investigated.
authors.affiliation: AG Tumorgenetik der Medizinischen Fakultät, Martin-Luther-Universität Halle-Wittenberg, Halle/Saale, Germany.
authors.forename: Undraga
authors.initials: U
authors.lastname: Schagdarsurengin
authors.forename: Oliver
authors.initials: O
authors.lastname: Gimm
authors.forename: Henning
authors.initials: H
authors.lastname: Dralle
authors.forename: Cuong
authors.initials: C
authors.lastname: Hoang-Vu
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dammann
mesh_terms: D002277:Carcinoma / Q000235:genetics*; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D013964:Thyroid Neoplasms / Q000235:genetics*