RET Copy Number Alteration in Medullary Thyroid Cancer Is a Rare Event Correlated with RET Somatic Mutations and High Allelic Frequency
Autor: | Raffaele Ciampi, Liborio Torregrossa, Valeria Bottici, Rossella Elisei, Fulvio Basolo, Virginia Cappagli, Chiara Mulè, Teresa Ramone, Paolo Piaggi, Alessandro Prete, Antonio Matrone, Cristina Romei |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Male endocrine system diseases Somatic cell DNA Mutational Analysis Thyroid Gland medicine.disease_cause medullary thyroid cancer 0302 clinical medicine Gene Frequency Copy-number variation Genetics (clinical) Mutation RET copy number variation Medullary thyroid cancer Prognosis MLPA 030220 oncology & carcinogenesis Thyroidectomy congenital hereditary and neonatal diseases and abnormalities endocrine system DNA Copy Number Variations lcsh:QH426-470 Biology Polymorphism Single Nucleotide Article Disease-Free Survival 03 medical and health sciences Germline mutation Genetics medicine Biomarkers Tumor Humans Genetic Predisposition to Disease Multiplex ligation-dependent probe amplification Genetic Testing Thyroid Neoplasms Allele Allele frequency Proto-Oncogene Proteins c-ret medicine.disease Carcinoma Neuroendocrine lcsh:Genetics 030104 developmental biology Cancer research Neoplasm Recurrence Local Follow-Up Studies |
Zdroj: | Genes, Vol 12, Iss 35, p 35 (2021) Genes Volume 12 Issue 1 |
ISSN: | 2073-4425 |
Popis: | 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. |
Databáze: | OpenAIRE |
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