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 RET 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 RET gene CNV prevalence and their potential role in MTC development. RET 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 RET 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 RET gene cases (aneuploid) was higher in RET positive tumors. Aneuploid cases also showed a higher allelic frequency of the RET 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. RET gene CNVs are rare events in sporadic MTC and are associated with RET somatic mutation, suggesting that they could not be a driver mechanism of tumoral transformation per se. Finally, we found a positive correlation between RET gene CNV and a worse clinical outcome. View Full-Text

Keywords: medullary thyroid cancer; RET; copy number variation; MLPA

▼ Show Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Share and Cite

MDPI and ACS Style

Ramone, T.; Mulè, C.; Ciampi, R.; Bottici, V.; Cappagli, V.; Prete, A.; Matrone, A.; Piaggi, P.; Torregrossa, L.; Basolo, F.; Elisei, R.; Romei, C. RET Copy Number Alteration in Medullary Thyroid Cancer Is a Rare Event Correlated with RET Somatic Mutations and High Allelic Frequency. Genes 2021, 12, 35. https://doi.org/10.3390/genes12010035

AMA Style

Ramone T, Mulè C, Ciampi R, Bottici V, Cappagli V, Prete A, Matrone A, Piaggi P, Torregrossa L, Basolo F, Elisei R, Romei C. RET Copy Number Alteration in Medullary Thyroid Cancer Is a Rare Event Correlated with RET Somatic Mutations and High Allelic Frequency. Genes. 2021; 12(1):35. https://doi.org/10.3390/genes12010035

Chicago/Turabian Style

Ramone, Teresa, Chiara Mulè, Raffaele Ciampi, Valeria Bottici, Virginia Cappagli, Alessandro Prete, Antonio Matrone, Paolo Piaggi, Liborio Torregrossa, Fulvio Basolo, Rossella Elisei, and Cristina Romei. 2021. "RET Copy Number Alteration in Medullary Thyroid Cancer Is a Rare Event Correlated with RET Somatic Mutations and High Allelic Frequency" Genes 12, no. 1: 35. https://doi.org/10.3390/genes12010035

Find Other Styles

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Abstract views Pdf views Html views

Article Menu

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

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Article Access Map by Country/Region

Further Information

Guidelines

MDPI Initiatives

Follow MDPI