Gene-specific promoter hypermethylation without global hypomethylation in follicular thyroid cancer.
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.
Lee
Jia-Jing
JJ
Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, CMM L8:01, SE-171 76 Stockholm, Sweden. jia.jing.lee@ki.se
Geli
Janos
J
Larsson
Catharina
C
Wallin
Göran
G
Karimi
Mohsen
M
Zedenius
Jan
J
Höög
Anders
A
Foukakis
Theodoros
T
D018263:Adenocarcinoma, Follicular / Q000235:genetics*; D000328:Adult; D000368:Aged; D002648:Child; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D013964:Thyroid Neoplasms / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics
C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins