title: EZH2 and ZFX oncogenes in malignant behaviour of parathyroid neoplasms.
abstract: Several studies reported somatic mutations of many genes (MEN1, CTNNB1, CDKIs and others) in parathyroid adenoma, although with different prevalence. Recently, activating mutations of the EZH2 and ZFX oncogenes were identified in benign parathyroid adenoma by whole exome sequencing. The same mutations had been found in blood and ovary malignant tumours. On one hand, this result raised the hypothesis that these oncogenes may play a role in the onset of parathyroid tumour, but it would also suggest they may be involved in malignant, rather benign, parathyroid neoplasm. Our aim was to verify the occurrence of selected mutations of the EZH2 and ZFX genes in an Italian cohort of 23 sporadic parathyroid carcinomas, 12 atypical and 45 typical adenomas. DNA was extracted from paraffin-embedded tissues, PCR amplified and directly sequenced. No mutations were detected in the coding sequence and boundaries of both genes in any of the samples. Two polymorphisms of the EZH2 gene were identified with different prevalence: the rs2072407 variant was present in the 30 % of the samples, in keeping with the overall frequency in larger populations, while the rs78589034 variant, located close to the 5' end of the exon 16, was detected in only one proband with familial isolated hyperparathyroidism; we investigated the possible outcome on the splicing process. EZH2 and ZFX genes do not seem to have an impact on the onset of most parathyroid tumours, both benign and malignant, though further studies on larger cohorts of different ethnicity are needed.
authors.affiliation: Medical Genetics, Poliambulatorio Giovanni Paolo II, IRCCS Casa Sollievo della Sofferenza Hospital, 71013, San Giovanni Rotondo, FG, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Sanpaolo
authors.affiliation: Medical Genetics, Poliambulatorio Giovanni Paolo II, IRCCS Casa Sollievo della Sofferenza Hospital, 71013, San Giovanni Rotondo, FG, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Miroballo
authors.affiliation: Endocrinology Unit, Department of Biomedical Sciences for Health, University of Milan, IRCCS Policlinico San Donato, San Donato Milanese, MI, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Corbetta
authors.affiliation: Laboratory of Molecular Biology, IRCCS Policlinico San Donato, San Donato Milanese, MI, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Verdelli
authors.affiliation: Medical Genetics, Poliambulatorio Giovanni Paolo II, IRCCS Casa Sollievo della Sofferenza Hospital, 71013, San Giovanni Rotondo, FG, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Baorda
authors.affiliation: Laboratory of Oncology, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Balsamo
authors.affiliation: Pathology, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Graziano
authors.affiliation: Laboratory of Oncology, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.
authors.forename: F P
authors.initials: FP
authors.lastname: Fabrizio
authors.affiliation: Medical Genetics, Poliambulatorio Giovanni Paolo II, IRCCS Casa Sollievo della Sofferenza Hospital, 71013, San Giovanni Rotondo, FG, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Cinque
authors.affiliation: Endocrinology, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Scillitani
authors.affiliation: Laboratory of Oncology, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.
authors.forename: L A
authors.initials: LA
authors.lastname: Muscarella
authors.affiliation: Medical Genetics, Poliambulatorio Giovanni Paolo II, IRCCS Casa Sollievo della Sofferenza Hospital, 71013, San Giovanni Rotondo, FG, Italy. v.guarnieri@operapadrepio.it.
authors.forename: Vito
authors.initials: V
authors.lastname: Guarnieri
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000483:Alleles; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D006961:Hyperparathyroidism / Q000235:genetics* / Q000473:pathology; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009857:Oncogenes / Q000235:genetics; D010280:Parathyroid Glands / Q000473:pathology; D010282:Parathyroid Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D051741:Kruppel-Like Transcription Factors; C062076:zinc finger protein, X-linked; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein
keywords: Atypical adenoma; EZH2; Parathyroid carcinoma; ZFX