Abstract 2775: Characterization of transcriptional and epigenetic signatures of benign thyroid adenomas: Can we improve preoperative diagnosis of thyroid nodules

Abstract

Abstract Introduction: It has been estimated that as many as 50,000 patients in the United States receive unnecessary thyroidectomies due to the inability to distinguish benign thyroid nodules from malignant ones. Up to 30% of fine needle aspirates performed for thyroid nodules diagnosis are indeterminate due to overlapping cytological features between benign and malignant nodules. At present, commercially-available diagnostic tests for thyroid nodules are based on the molecular differences observed between thyroid cancer compared to normal thyroid tissue. However, the molecular signature of benign thyroid nodules is neither well-characterized nor included in currently available diagnostic panels. The objective of this study was to determine whether thyroid adenomas (TA) are distinct from normal thyroid tissue and papillary thyroid cancer (PTC). Methods: Whole transcriptome analysis was used to assess differences in transcriptional activity in 9 TA and 12 PTC tissue pairs (with matched normal adjacent thyroid tissue from the same patients). In order to evaluate epigenetic alterations associated with TA development, we used reduced representation bisulfite sequencing (RRBS) in 114 thyroid specimens (40 PTC, 28 TA and 46 matching adjacent thyroid tissues). This approach provides single base resolution of DNA methylation genome wide. Results: According to our data, transcriptome activity divided analyzed specimens into three separate groups: PTC, TA and adjacent thyroid tissues. TA demonstrated a unique transcriptional pattern, distinct from both normal adjacent thyroid tissue and PTC. Similar results were obtained by analysis of epigenetic alterations in these tissues. According to the clustering analysis of DNA methylation patterns, the majority (18 of 28) of benign nodules forms a separate cluster, distinct from adjacent normal thyroid and PTC tissue clusters. Within this group, 14 of 28 TA demonstrated a distinct DNA methylation signature associated with TA-specific hypermethylation. In fact, only 4 of 28 TA demonstrated a DNA methylation signature similar to normal thyroid tissue, suggesting that the majority of TA is not equivalent to normal thyroid. Conclusion: According to whole transcriptome analysis and genome wide analysis of DNA methylation, TA is frequently associated with specific transcriptional and DNA methylation signatures compared to normal thyroid tissue and PTC. These data indicate that the majority of thyroid adenomas are associated with a unique molecular pathway that is distinct from PTC development. Use of the adenoma-specific molecular signature can be an essential factor in the improvement of PTC diagnostic panels, helping to reduce unnecessary thyroidectomies. Citation Format: Audrey H. Choi, Ryan Lew, Michael O’Leary, Yuman Fong, John H. Yim, Maria A. Hahn. Characterization of transcriptional and epigenetic signatures of benign thyroid adenomas: Can we improve preoperative diagnosis of thyroid nodules. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2775.