Abstract
Background: Epigenetic regulation plays a significant role in oncogenesis of different organs. However, the role of methylation in thyroid carcinoma is largely unexplored.
Methods: We carried out a genome-wide methylation assay for a total of 40 thyroid carcinoma patients (m=12, f=28) and compared them with corresponding normal thyroid tissue from the same individual using Illumina's Infinium HumanMethylation450 BeadChip. Histologically, a total of 29 patients had papillary carcinoma (PC), 4 had follicular carcinoma (FC) and 7 had follicular variant of papillary carcinoma (FVPC). The methylation assay covered a total of 485,577 loci across the genome of which 150,254 are on CpG island, 112,067 are on shore (0-2kb from CpG island), 47,144 are on shelf (2-4 kb from CpG island) and the rest 176,112 are in the deep sea (>4kb from the CpG island).
Result: We used mixed model 3-way ANOVA to identify differentially methylated loci (DML) between tumor and corresponding normal tissue, where the beta value (degree of methylation) was adjusted for person to person variation and gender. In PC and FVPC, we identified a total of 1151 and 150 tumor related DML respectively that were significant at FDR 0.05 and absolute difference of methylation (Δ beta) of 0.2. In FC, none was significant after the correction for multiple testing. Comparing the list of DML from PC and FVPC, we identified (a) 35 DML which were common in all histological types of thyroid cancer, (b) 115 DML that were specific to FVPC and (c) 1116 DML that were specific to PC. It was seen that irrespective of the histological type, Transforming Growth Factor Beta 1 (TGFB1) gene was hypermethylated in thyroid carcinoma. The Neuralized Homolog 1B (NEURL1B) gene was specifically hypermethylated in FVPC. A number of genes were specifically differentially methylated only in PC including BCL7C, LPAR5, ACOX3 and also micro RNA 762 among others. In case of the common DML (those are found in all histological types), a large proportion (77.14%) were in the deep sea. In the same line among the PC specific DML, similar proportion were also in the deep sea (70.07%). But among the FVPC specific DML, considerable proportion were on the CpG island and shores (46.95%) indicating the significance of changes in the promoter methylation status in this particular histological subtype of thyroid carcinoma.
Conclusion: For the first time, we present comprehensive genome-wide methylation profile in thyroid carcinoma and our data suggests that differential methylation may be associated with different histological subtypes.
Citation Format: Farzana Jasmine, Mosiur Rahman, Shantanu Roy, Mohammed Kamal, Habibul Ahsan, Muhammad G. Kibriya. Genome-wide methylation profile in thyroid carcinoma. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A55.
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