Hypermethylation of the Pendred syndrome gene SLC26A4 is an early event in thyroid tumorigenesis.
Expression of the recently cloned Pendred syndrome gene SLC26A4 or PDS has been found to be decreased or even absent in various thyroid tumors. To explore the underlying mechanism, we conducted DNA sequencing and methylation-specific PCR studies in 64 primary thyroid tumors and 6 thyroid cell lines. We found aberrant hypermethylation of the SLC26A4 gene in 44% of histologically benign adenomas, 46% of follicular thyroid cancers, 71% of papillary thyroid cancers, 71% of anaplastic thyroid cancers, and 100% of cell lines. A reciprocal relationship between methylation and expression of the gene was confirmed in cell lines and thyroid tissues. We have thus demonstrated epigenetic changes as a new mechanism in altering the SLC26A4 gene function, in addition to genetic mutation in Pendred syndrome. SLC26A4 gene methylation in benign adenomas and the relatively well-differentiated WRO cell line suggest that this alteration is an early event in thyroid tumorigenesis.
Division of Endocrinology and Metabolism, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Mingzhao
M
Xing
Yutaka
Y
Tokumaru
Guojun
G
Wu
William B
WB
Westra
Paul W
PW
Ladenson
David
D
Sidransky
D002352:Carrier Proteins / Q000235:genetics*; D019175:DNA Methylation; D020868:Gene Silencing; D006801:Humans; D026901:Membrane Transport Proteins; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000076988:Sulfate Transporters; D013964:Thyroid Neoplasms / Q000235:genetics*; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters