title: TERT Promoter Mutations in Papillary Thyroid Microcarcinomas.
abstract: BACKGROUND
  Small papillary thyroid carcinomas have contributed to the worldwide increased incidence of differentiated thyroid cancer observed over the past decades. However, the mortality rate has not changed over the same period of time, raising questions about the possibility that thyroid cancer patients, especially those with small tumors, are overdiagnosed and overtreated. Molecular prognostic marker able to discriminate aggressive thyroid cancers from those with an indolent course would be of great relevance to tailor the therapeutic approach and reduce overtreatment. Mutations in the TERT promoter were recently reported to correlate strongly with aggressiveness in advanced forms of thyroid cancer, holding promise for a possible clinical application. The occurrence and potential clinical relevance of TERT mutations in papillary thyroid microcarcinomas (mPTCs) is currently unknown. This study aimed to analyze the occurrence of two TERT promoter mutations (-124C>T and -146C>T) and their potential association with unfavorable clinical features in a large cohort of mPTCs.
  
  
  METHODS
  A total of 431 mPTCs cases were collected from six Italian institutions, and TERT promoter mutational status was assessed by a next-generation sequencing approach.
  
  
  RESULTS
  TERT promoter mutations were found in 4.7% of the analyzed mPTCs, showing that even microcarcinomas carry mutations in this gene. Correlation analysis showed that TERT promoter mutations are not associated with aggressive features or clinical outcome in the cohort analyzed.
  
  
  CONCLUSIONS
  TERT mutations are present but uncommon in mPTCs. Apparently, in mPTCs, the occurrence of TERT mutations is not correlated with unfavorable clinical features.
authors.affiliation: 1 Department of Medicine (DIMES), Anatomic Pathology Unit, Bellaria Hospital, University of Bologna , Bologna, Italy .
authors.forename: Dario
authors.initials: D
authors.lastname: de Biase
authors.affiliation: 2 Laboratory of Translational Research , Arcispedale S. Maria Nuova-IRCCS, Reggio Emilia, Italy .
authors.forename: Greta
authors.initials: G
authors.lastname: Gandolfi
authors.affiliation: 3 Pathology Unit, Department of Oncology , Arcispedale S. Maria Nuova-IRCCS, Reggio Emilia, Italy .
authors.forename: Moira
authors.initials: M
authors.lastname: Ragazzi
authors.affiliation: 4 Division of Endocrinology and Nephrology, University of Leipzig , Leipzig, Germany .
authors.forename: Markus
authors.initials: M
authors.lastname: Eszlinger
authors.affiliation: 2 Laboratory of Translational Research , Arcispedale S. Maria Nuova-IRCCS, Reggio Emilia, Italy .
authors.forename: Valentina
authors.initials: V
authors.lastname: Sancisi
authors.affiliation: 2 Laboratory of Translational Research , Arcispedale S. Maria Nuova-IRCCS, Reggio Emilia, Italy .
authors.forename: Mila
authors.initials: M
authors.lastname: Gugnoni
authors.affiliation: 5 Department of Pharmacology and Biotechnology (FaBiT), University of Bologna , Bologna, Italy .
authors.forename: Michela
authors.initials: M
authors.lastname: Visani
authors.affiliation: 5 Department of Pharmacology and Biotechnology (FaBiT), University of Bologna , Bologna, Italy .
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pession
authors.affiliation: 6 Anatomic Pathology Unit, AUSL Bologna-Maggiore Hospital , Bologna, Italy .
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Casadei
authors.affiliation: 7 Department of Internal Medicine, University la Sapienza , Rome, Italy .
authors.forename: Cosimo
authors.initials: C
authors.lastname: Durante
authors.affiliation: 8 Department of Health Science, University Magna Grecia di Catanzaro , Catanzaro, Italy .
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Costante
authors.affiliation: 9 Endocrinology Unit, Tinchi-Pisticci, Matera, Italy .
authors.forename: Rocco
authors.initials: R
authors.lastname: Bruno
authors.affiliation: 10 Department of Medical Science , Ospedale Casa Sollievo della Sofferenza-IRCCS, San Giovanni Rotondo, Italy .
authors.forename: Massimo
authors.initials: M
authors.lastname: Torlontano
authors.affiliation: 4 Division of Endocrinology and Nephrology, University of Leipzig , Leipzig, Germany .
authors.forename: Ralf
authors.initials: R
authors.lastname: Paschke
authors.affiliation: 7 Department of Internal Medicine, University la Sapienza , Rome, Italy .
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Filetti
authors.affiliation: 3 Pathology Unit, Department of Oncology , Arcispedale S. Maria Nuova-IRCCS, Reggio Emilia, Italy .
authors.forename: Simonetta
authors.initials: S
authors.lastname: Piana
authors.affiliation: 11 Endocrinology Unit, Arcispedale S. Maria Nuova-IRCCS, Reggio Emilia, Italy .
authors.forename: Andrea
authors.initials: A
authors.lastname: Frasoldati
authors.affiliation: 1 Department of Medicine (DIMES), Anatomic Pathology Unit, Bellaria Hospital, University of Bologna , Bologna, Italy .
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tallini
authors.affiliation: 2 Laboratory of Translational Research , Arcispedale S. Maria Nuova-IRCCS, Reggio Emilia, Italy .
authors.forename: Alessia
authors.initials: A
authors.lastname: Ciarrocchi
mesh_terms: D000328:Adult; D000483:Alleles; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000628:therapy; D015331:Cohort Studies; D019295:Computational Biology; D004252:DNA Mutational Analysis; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015994:Incidence; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000628:therapy
chemical_list: C509186:TERT protein, human; D019098:Telomerase