title: Chromosome 10 and RET gene copy number alterations in hereditary and sporadic Medullary Thyroid Carcinoma.
abstract: About 30% of hereditary Medullary Thyroid Carcinoma (MTC) have been demonstrated to harbour imbalance between mutant and wild-type RET alleles. We studied the RET copy number alterations (RET CNA) in 65 MTC and their correlation with RET mutation and patients' outcome. Fluorescence in situ Hybridization and Real-time PCR revealed RET CNA in 27.7% MTC but only in a variable percentage of cells. In sporadic MTC, RET CNA were represented by chromosome 10 aneuploidy while in hereditary MTC by RET amplification. A significant higher prevalence of RET CNA was observed in RET mutated MTC (P=0.003). RET CNA was also associated to a poorer outcome (P=0.005). However, the multivariate analysis revealed that only RET mutation and advanced clinical stage correlated with the worst outcome. In conclusion, 30% MTC harbour RET CNA in variable percentage of cells suggesting cell heterogeneity. RET CNA can be considered a poor prognostic factor potentiating the poor prognostic role of RET mutation.
authors.affiliation: Department of Endocrinology and Metabolism, University-Hospital of Pisa, 56100 Pisa, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Ciampi
authors.forename: Cristina
authors.initials: C
authors.lastname: Romei
authors.forename: Barbara
authors.initials: B
authors.lastname: Cosci
authors.forename: Agnese
authors.initials: A
authors.lastname: Vivaldi
authors.forename: Valeria
authors.initials: V
authors.lastname: Bottici
authors.forename: Giulia
authors.initials: G
authors.lastname: Renzini
authors.forename: Clara
authors.initials: C
authors.lastname: Ugolini
authors.forename: Alessia
authors.initials: A
authors.lastname: Tacito
authors.forename: Fulvio
authors.initials: F
authors.lastname: Basolo
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinchera
authors.forename: Rossella
authors.initials: R
authors.lastname: Elisei
mesh_terms: D000328:Adult; D000368:Aged; D018276:Carcinoma, Medullary / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D018278:Carcinoma, Neuroendocrine; D002879:Chromosomes, Human, Pair 10; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D040941:Heredity; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D011379:Prognosis; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D055815:Young Adult
chemical_list: D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human