ECE2013 Oral Communications Thyroid (6 abstracts)
DNA methylation signatures identify biologically distinct thyroid cancer subtypes
Juan Luis Fernandez-Morera 1, , Sandra Rodriguez-Rodero 2 , Elias Delgado Alvarez 1 , Agustin Fernandez-Fernandez 2 , Ivan Fernandez-Vega 4 , Rocio Gonzalez-Marquez 3 , Veronica Sanchez-Rivas 1 , Lorena Suarez-Gutierrez 1 , Maria Galiana Rodriguez Caballero 1 , Jessica Ares Blanco 1 , Mario Fernandez-Fraga 2 & Edelmiro Menendez-Torre 1
1Endocrinology and Nutrition Service, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain; 2Cancer Epigenetics Laboratory, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, Oviedo, Asturias, Spain; 3Otolaryngology Service, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain; 4Pathology Service, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain.
Introduction: The global patterns of aberrant DNA methylation in thyroid cancer are not known. In this study, we have used DNA methylation arrays to determine, for the first time, the genome-wide promoter methylation status of different subtypes of thyroid tumors.
Material and methods: We analyzed a cohort of 54 snap frozen thyroid samples (thirteen papillary tumors, six follicular, eleven anaplastic, twenty medullar and four normal tissue samples). Also human thyroid carcinoma-derived cell lines, K1, FTC-133, 8305C and TT were obtained from the ECACC to analyze. A microarray-based DNA methylation profiling was performed with the Illumina Infinium Human Methylation 27K Platform with some of these samples. Hierarchical cluster analysis and definition of differentially methylated genes, computational gene expression analysis and gene ontology analysis of differentially methylated genes were preformed. To confirm those data, bisulfite pyrosequening of several genes were also done. Also proportions of PcG-marks and bivalent domains in different methylation groups were studied.
Results: We identified 262 and 352 hyper and 13 and 21 hypomethylated genes in differentiated papillary and follicular tumors respectively. Surprisingly, undifferentiated tumors displayed more hypomethylated genes (280 in anaplastic, 393 in medullar) than aberrantly hypermethylated genes (86 in anaplastic, 131 in medullar). Hypermethylated genes in tumors originating from follicular cells were preferentially involved in developmental processes whilst those in medullary tumors were primarily involved in cell signaling and iodium pathways. Hypomethylated genes were enriched in immune system functions. Among the genes identified, we show that four potential tumor suppressor genes (ADAMTS8, HOXB4, ZIC1, and KISS1R) and four potential oncogenes (INSL4, DPPA2, TCL1B, and NOTCH4) are frequently regulated by aberrant methylation in thyroid tumors. Further studies are needed to determine the potential clinical interest of the tumor subtype-specific DNA methylation signatures described herein and the role of aberrant promoter hypomethylation in undifferentiated thyroid tumors.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more