RET Copy Number Alteration in Medullary Thyroid Cancer Is a Rare Event Correlated with RET Somatic Mutations and High Allelic Frequency.

Copy number variations (CNV) of the gene have been described in 30% of Medullary Thyroid Cancer (MTC), but no information is available about their role in this tumor. This study was designed to clarify gene CNV prevalence and their potential role in MTC development. gene CNV were analyzed in 158 sporadic MTC cases using the ION Reporter Software (i.e., in silico analysis) while the multiplex ligation-dependent probe amplification assay (i.e., in vitro analysis) technique was performed in 78 MTC cases. We identified three categories of ploidy: 137 in 158 (86.7%) cases were diploid and 21 in 158 (13.3%) were aneuploid. Among the aneuploid cases, five out of 21 (23.8%) showed an allelic deletion while 16 out of 21 (76.2%) had an allelic amplification. The prevalence of amplified or deleted gene cases (aneuploid) was higher in positive tumors. Aneuploid cases also showed a higher allelic frequency of the driver mutation. The prevalence of patients with metastatic disease was higher in the group of aneuploid cases while the higher prevalence of disease-free patients was observed in diploid tumors. A statistically significant difference was found when comparing the ploidy status and mortality. gene CNVs are rare events in sporadic MTC and are associated with somatic mutation, suggesting that they could not be a driver mechanism of tumoral transformation per se. Finally, we found a positive correlation between gene CNV and a worse clinical outcome.