Effects of Single Nucleotide Variations, Gene Rearrangements, and Numerical Changes on Thyroid Cancer Pathogenesis: A Narrative Review
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S Hosseinzadeh , S Pakizehkar , MA Daneshpour , M Hedayati |
Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, I.R. Iran , hedayati47@gmail.com |
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Abstract: (615 Views) |
Thyroid cancer is the most common endocrine malignancy. Molecular analysis of thyroid tumors has shown that the cause of its development, as with other cancers, is the accumulation of genetic and epigenetic changes along with progressive disorders. This study aimed to provide a comprehensive overview of the genetic alterations related to the pathogenesis of thyroid cancer. For this purpose, PubMed and Science Direct databases were searched from the beginning of 2018 to January 5, 2022, to investigate the relationship between genetic alterations and the pathogenesis of thyroid cancers. The keywords used included a combination of “Thyroid cancer/carcinoma/neoplasm” AND “pathogenesis” AND “genetic alterations”. The results showed that the most frequently reported genetic modifications included independent mutations, especially in the BRAF, RAS, TERT, and TP53 genes, gene rearrangements, especially in the RET, TRK, BRAF, and PAX8/PPARγ genes, numerical changes, and common co-mutations. The connection between these changes and numerous secondary molecular changes leads to the strengthening and synergy of their effects on the molecular pathogenesis of cancer. In addition, genes involved in DNA repair, signal transmission, and cell cycle control are affected more by genetic alterations, and mutations in the mitogen-activated protein kinase (MAPK) pathway and somatic mutations in the genes involved in the PI3K-AKT pathway lead to tumorigenesis and its progression in most cases. Therefore, secondary molecular disorders and simultaneous genetic alterations lead to synergism and genetic enhancement in thyroid tumorigenesis. A better understanding of the molecular pathogenesis and the discovery and recognition of markers can provide prognosis and realize potential clinical solutions for managing and treating thyroid cancer. |
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Keywords: Thyroid Neoplasms, Carcinogenesis, MAPK, Mutation, AKT, PI3K, Nucleotides, Pathogenesis |
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Full-Text [PDF 1054 kb]
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Type of Study: Review |
Subject:
Endocrinology Received: 2023/02/10 | Accepted: 2023/07/18 | Published: 2023/03/1
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