Chromosome 10 and RET gene copy number alterations in hereditary and sporadic Medullary Thyroid Carcinoma

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.

► We analyzed presence of RET copy number alterations (RET CNA) in 65 MTC (12 hereditary, 53 sporadic). ► We found RET CNA in 27.7% MTC and they were present only in a variable percentage of cells. ► In sporadic MTC, RET CNA were represented by chromosome 10 aneuploidy. ► In hereditary MTC, RET CNA were represented by RET amplification. ► RET not-mutated MTC, showed statistically significant correlation between RET CNA and poorer outcome.