Gene-specific promoter hypermethylation without global hypomethylation in follicular thyroid cancer

Jia Jing Lee, Janos Geli, Catharina Larsson, Göran Wallin, Mohsen Karimi, Jan Zedenius, Anders Höög, Theodoros Foukakis

Research output: Contribution to journalArticlepeer-review


Genome-wide hypomethylation and hypermethylation at CpG promoters are common in cancer. To date, little is known about global methylation changes in follicular thyroid cancer (FTC). Two independent quantitative methods, bisulphite Pyrosequencing of Long Interspersed Nucleotide Elements-1 (LINE-1) and LUminometric Methylation Assay (LUMA) were used to quantify genome-wide methylation in 21 FTC and corresponding normal thyroid tissues. Unexpectedly global methylation was not found significantly altered in tumors compared to normal thyroid by either LINE-1 (p=0.57) or LUMA (p=0.42), whilst the promoter of a tumor suppressor that is often epigenetically dysregulated, RASSF1A was found to be significantly hypermethylated by Pyrosequencing (p=0.0001). Moreover, allelic imbalance at the RASSF1A locus was observed in 15/21 of the tumors. mRNA expression of RASSF1A was significantly lower in tumors compared to corresponding normal tissues (p=0.0002). In summary, the epigenetic inactivation of RASSF1A is a frequent event in FTC, but is not coupled to changes in global methylation.

Original languageEnglish (US)
Pages (from-to)861-869
Number of pages9
JournalInternational journal of oncology
Issue number4
StatePublished - Oct 2008
Externally publishedYes


  • Follicular thyroid cancer
  • Gene-specific promoter hypermethylation
  • LINE-1 methylation
  • LUMA

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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