A Genome-Wide Screening of Promoter DNA Methylation Reveals Differential Profiles of Follicular-Cell Derived Thyroid Neoplasms.
Tetsuo Kondo, Tadao Nakazawa, Tomonori Kawasaki, Kunio Mochizuki, Dong-Feng Niu, Tetsu Yamane, Ryohei Katoh. University of Yamanashi, Chuo, Japan
Background: Thyroid cancer show wide spectrum of differentiation from indolent well-differentiated carcinomas to lethal undifferentiated carcinoma. This spectrum of progression has been linked with a pattern of cumulative intragenic defects that correlates with tumor differentiation, aggressiveness, and metastatic potential. Recent advances have further disclosed the significance of epigenetic alterations in the development and progression of human cancers.
Design: In this study, we analyzed a global DNA methylation in human thyroid carcinomas (papillary carcinoma, 5cases; undifferentiated carcinoma, 2 cases) as compared to normal thyroid tissues (5 cases), and 6 thyroid cancer cell lines (TPC-1, KTC-1, WRO, 8505C, ASH-3 and KMH-2) using Illumina Beadchip (HumanMethylation27). Quantitive measurements of promoter DNA methylation were determined for 27,578 target CpG sites spanning a total of 14,495 genes. DNA methylation profiles were analyzed by Gene Cluster 3.0 and Java Treeview software.
Results: There were 866 genes that showed significantly increased or decreased promoter methylation in thyroid carcinomas and thyroid carcinoma cell lines. Using these genes for cluster analysis, we found differential epigenetic profiles among thyroid cancer. Three distinct patterns of aberrant methylation were identified. The first gene group showed stepwise hypermethylation among normal thyroid, papillary carcinoma and undifferentiated carcinoma. The second gene group demonstrated hypermethylation especially in undifferentiated carcinoma. The third gene group exhibited hypermethylation in normal thyroid, meanwhile hypomethylation in undifferentiated carcinoma. Methylation status of thyroid cancer cell lines was similar to undifferentiated carcinoma tissues.
Conclusions: We concluded that methylation status of certain subsets of genes were associated with histological types of thyroid cancer. Our data suggested the involvement of epigenetic events in the progression of thyroid carcinoma, and also provide a basis of molecular targets for epigenetic therapy in thyroid cancer.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 44, Tuesday Afternoon