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DNA Methylation in Thyroid Tumorigenesis
Department of Otolaryngology/Head and Neck Surgery, Henry Ford Hospital, Detroit, MI 48202, USA
Department of Pathology, Henry Ford Hospital, Detroit, MI 48202, USA
Essex Surgical Associates, PC, Beverly, MA 01915, USA
* Author to whom correspondence should be addressed.
Received: 14 January 2011; in revised form: 16 March 2011 / Accepted: 21 March 2011 / Published: 29 March 2011
Abstract: Thyroid cancer is the most common endocrine cancer with 1,690 deaths each year. There are four main types of which the papillary and follicular types together account for >90% followed by medullary cancers with 3% to 5% and anaplastic carcinomas making up < 3%. Epigenetic events of DNA hypermethylation are emerging as promising molecular targets for cancer detection. Our immediate and long term goal is to identify DNA methylation markers for early detection of thyroid cancer. This pilot study comprised of 21 patients to include 11 papillary thyroid cancers (PTC), 2 follicular thyroid cancers (FTC), 5 normal thyroid cases, and 3 hyperthyroid cases. Aberrant promoter methylation was examined in 24 tumor suppressor genes using the methylation specific multiplex ligation-dependent probe amplification (MS-MLPA) assay and in the NIS gene using methylation-specific PCR (MSP). The frequently methylated genes were CASP8 (17/21), RASSF1 (16/21) and NIS (9/21). In the normal samples, CASP8, RASSF1 and NIS were methylated in 5/5, 4/5 and 1/5 respectively. In the hyperthyroid samples, CASP8, RASSF1 and NIS were methylated in 3/3, 2/3 and 1/3 respectively. In the thyroid cancers, CASP8, RASSF1, and NIS were methylated in 9/13, 10/13, and 7/13 respectively. CASP8, RASSF1 and NIS were also methylated in concurrently present normal thyroid tissue in 3/11, 4/11 and 3/11 matched thyroid cancer cases (matched for presence of both normal thyroid tissue and thyroid cancer), respectively. Our data suggests that aberrant methylation of CASP8, RASSF1, and NIS maybe an early change in thyroid tumorigenesis regardless of cell type.
Keywords: papillary thyroid cancer; follicular thyroid cancer; hypermethylation; NIS; CASP8; RASSF1
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Stephen, J.K.; Chitale, D.; Narra, V.; Chen, K.M.; Sawhney, R.; Worsham, M.J. DNA Methylation in Thyroid Tumorigenesis. Cancers 2011, 3, 1732-1743.
Stephen JK, Chitale D, Narra V, Chen KM, Sawhney R, Worsham MJ. DNA Methylation in Thyroid Tumorigenesis. Cancers. 2011; 3(2):1732-1743.
Stephen, Josena K.; Chitale, Dhananjay; Narra, Vinod; Chen, Kang Mei; Sawhney, Raja; Worsham, Maria J. 2011. "DNA Methylation in Thyroid Tumorigenesis." Cancers 3, no. 2: 1732-1743.