title: DNA methylation signatures identify biologically distinct thyroid cancer subtypes.
abstract: OBJECTIVE
  The purpose of this study was to determine the global patterns of aberrant DNA methylation in thyroid cancer.
  
  
  METHODS
  We have used DNA methylation arrays to determine, for the first time, the genome-wide promoter methylation status of papillary, follicular, medullary, and anaplastic thyroid tumors.
  
  
  RESULTS
  We identified 262 and 352 hypermethylated and 13 and 21 hypomethylated genes in differentiated papillary and follicular tumors, respectively. Interestingly, the other tumor types analyzed displayed more hypomethylated genes (280 in anaplastic and 393 in medullary tumors) than aberrantly hypermethylated genes (86 in anaplastic and 131 in medullary tumors). Among the genes indentified, we show that 4 potential tumor suppressor genes (ADAMTS8, HOXB4, ZIC1, and KISS1R) and 4 potential oncogenes (INSL4, DPPA2, TCL1B, and NOTCH4) are frequently regulated by aberrant methylation in primary thyroid tumors. In addition, we show that aberrant promoter hypomethylation-associated overexpression of MAP17 might promote tumor growth in thyroid cancer.
  
  
  CONCLUSIONS
  Thyroid cancer subtypes present differential promoter methylation signatures, and nondifferentiated subtypes are characterized by aberrant promoter hypomethylation rather than hypermethylation. Additional 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 nondifferentiated thyroid tumors.
authors.affiliation: Department of Endocrinology and Nutrition, Instituto Universitario de Oncología del Principado de Asturias, Hospital Universitario Central de Asturias, 33006 Oviedo, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Rodríguez-Rodero
authors.forename: Agustín F
authors.initials: AF
authors.lastname: Fernández
authors.forename: Juan Luís
authors.initials: JL
authors.lastname: Fernández-Morera
authors.forename: Patricia
authors.initials: P
authors.lastname: Castro-Santos
authors.forename: Gustavo F
authors.initials: GF
authors.lastname: Bayon
authors.forename: Cecilia
authors.initials: C
authors.lastname: Ferrero
authors.forename: Rocio G
authors.initials: RG
authors.lastname: Urdinguio
authors.forename: Rocío
authors.initials: R
authors.lastname: Gonzalez-Marquez
authors.forename: Carlos
authors.initials: C
authors.lastname: Suarez
authors.forename: Iván
authors.initials: I
authors.lastname: Fernández-Vega
authors.forename: Manuel Florentino
authors.initials: MF
authors.lastname: Fresno Forcelledo
authors.forename: Pablo
authors.initials: P
authors.lastname: Martínez-Camblor
authors.forename: Veronika
authors.initials: V
authors.lastname: Mancikova
authors.forename: Esmeralda
authors.initials: E
authors.lastname: Castelblanco
authors.forename: Marco
authors.initials: M
authors.lastname: Perez
authors.forename: Pablo Isidro
authors.initials: PI
authors.lastname: Marrón
authors.forename: Marta
authors.initials: M
authors.lastname: Mendiola
authors.forename: David
authors.initials: D
authors.lastname: Hardisson
authors.forename: Pilar
authors.initials: P
authors.lastname: Santisteban
authors.forename: Garcilaso
authors.initials: G
authors.lastname: Riesco-Eizaguirre
authors.forename: Xavier
authors.initials: X
authors.lastname: Matías-Guiu
authors.forename: Amancio
authors.initials: A
authors.lastname: Carnero
authors.forename: Mercedes
authors.initials: M
authors.lastname: Robledo
authors.forename: Elías
authors.initials: E
authors.lastname: Delgado-Álvarez
authors.forename: Edelmiro
authors.initials: E
authors.lastname: Menéndez-Torre
authors.forename: Mario F
authors.initials: MF
authors.lastname: Fraga
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018276:Carcinoma, Medullary / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018278:Carcinoma, Neuroendocrine; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D015331:Cohort Studies; D019175:DNA Methylation; D015536:Down-Regulation; D055106:Genome-Wide Association Study; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D000077273:Thyroid Cancer, Papillary; D065646:Thyroid Carcinoma, Anaplastic; D013961:Thyroid Gland / Q000378:metabolism* / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014015:Tissue Banks; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D009363:Neoplasm Proteins