Data from Comprehensive DNA Methylation Profiling of Medullary Thyroid Carcinoma: Molecular Classification, Potential Therapeutic Target, and Classifier System

作者：Cenkai Shen, Xiao Shi, Duo Wen, Yuqing Zhang, Yuxin Du, Yu Zhang, Ben Ma, Haitao Tang, Min Yin, Naisi Huang, Tian Liao, Ting-Ting Zhang, Chang’e Kong, Wenjun Wei, Qinghai Ji, Yu Wang · 年份：2024 · DOI：10.1158/1078-0432.c.7010464 · 研究领域：Thyroid Cancer Diagnosis and Treatment、Epigenetics and DNA Methylation、Glutathione Transferases and Polymorphisms

<div>AbstractPurpose:Medullary thyroid carcinoma (MTC) presents a distinct biological context from other thyroid cancers due to its specific cellular origin. This heterogeneous and rare tumor has a high prevalence of advanced diseases, making it crucial to address the limited therapeutic options and enhance complex clinical management. Given the high clinical accessibility of methylation information, we construct the largest MTC methylation cohort to date.Experimental Design:Seventy-eight fresh-frozen MTC samples constituted our methylation cohort. The comprehensive study process incorporated machine learning, statistical analysis, and in vitro experiments.Results:Our study pioneered the identification of a three-class clustering system for risk stratification, exhibiting pronounced epigenomic heterogeneity. The elevated overall methylation status in MTC-B, combined with the “mutual exclusivity” of hypomethylated sites displayed by MTC-A and MTC-C, distinctively characterized the MTC-specific methylation pattern. Integrating with the transcriptome, we further depicted the features of these three clusters to scrutinize biological properties. Several MTC-specific aberrant DNA methylation events were emphasized in our study. NNAT expression was found to be notably reduced in poor-prognostic MTC-C, with its promoter region overlapping with an upregulated differentially methylated region. &l...