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
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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