title: Epigenetic-related gene expression profile in medullary thyroid cancer revealed the overexpression of the histone methyltransferases EZH2 and SMYD3 in aggressive tumours.
abstract: Epigenetic control of gene expression plays a major influence in the development and progression of many cancer types. Aim of the present study was to investigate the expression of epigenetic regulators in a large cohort of medullary thyroid carcinomas (MTC), correlating the data with the clinical outcome and mutational status of the patients. Taqman Low Density Arrays (TLDAs) were used to analyze expression levels of several genes involved in the epigenetic control of transcription in a series of 54 MTCs. The patients cohort included 13 familial MTCs and 41 sporadic forms; 33 hosted a RET mutation and 13 a RAS somatic mutation. The expression profiling revealed in the more aggressive diseases (i.e. occurrence of metastases; persistent disease; disease-related death) a significant increase of EZH2 and SMYD3 gene expression. The increased levels of EZH2 and SMYD3 did not correlate significantly with mutational status of RET or RAS genes. Thus, the histone methyltransferases EZH2 and SMYD3 mRNA expression may represent useful prognostic biomarkers tailoring the most appropriate follow-up and timing of therapeutic approaches.
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche, Università di Roma "Sapienza", 00161 Roma, Italy.
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Sponziello
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche, Università di Roma "Sapienza", 00161 Roma, Italy.
authors.forename: Cosimo
authors.initials: C
authors.lastname: Durante
authors.affiliation: Institut Gustave Roussy, Université Paris Sud, 94805 Villejuif, France.
authors.forename: Amelie
authors.initials: A
authors.lastname: Boichard
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche, Università di Roma "Sapienza", 00161 Roma, Italy.
authors.forename: Mariavittoria
authors.initials: M
authors.lastname: Dima
authors.affiliation: Dipartimento di Scienze Mediche e Biologiche, Università di Udine, 33100 Udine, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Puppin
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche, Università di Roma "Sapienza", 00161 Roma, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Verrienti
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche, Università di Roma "Sapienza", 00161 Roma, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Tamburrano
authors.affiliation: Dipartimento di Scienze Chirurgiche, Università di Roma "Sapienza", 00161 Roma, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Di Rocco
authors.affiliation: Dipartimento di Scienze Chirurgiche, Università di Roma "Sapienza", 00161 Roma, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Redler
authors.affiliation: Institut Gustave Roussy, Université Paris Sud, 94805 Villejuif, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Lacroix
authors.affiliation: Institut Gustave Roussy, Université Paris Sud, 94805 Villejuif, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Bidart
authors.affiliation: Institut Gustave Roussy, Université Paris Sud, 94805 Villejuif, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Schlumberger
authors.affiliation: Dipartimento di Scienze Mediche e Biologiche, Università di Udine, 33100 Udine, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Damante
authors.affiliation: Dipartimento di Scienze della Salute, Università di Catanzaro, 88100 Catanzaro, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Russo
authors.affiliation: Dipartimento di Medicina Interna e Specialità Mediche, Università di Roma "Sapienza", 00161 Roma, Italy. Electronic address: sebastiano.filetti@uniroma1.it.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Filetti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018278:Carcinoma, Neuroendocrine; D002648:Child; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009361:Neoplasm Invasiveness; D063151:Polycomb Repressive Complex 2 / Q000235:genetics* / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2; C506278:SMYD3 protein, human
keywords: Epigenetics; Histone methylation; Medullary thyroid cancer; RAS; RET