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The Molecular Landscape of Hürthle Cell Thyroid Cancer Is Associated with Altered Mitochondrial Function—A Comprehensive Review

Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
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Cells 2020, 9(7), 1570; https://doi.org/10.3390/cells9071570
Received: 27 May 2020 / Revised: 21 June 2020 / Accepted: 25 June 2020 / Published: 27 June 2020
(This article belongs to the Special Issue Mitochondria, Metabolism and Cancer)
Hürthle cell thyroid carcinoma (HTC) accounts for 3–5% of all thyroid malignancies. Widely invasive HTC is characterized by poor prognosis and limited responsiveness to standard therapy with radioiodine. The molecular landscape of HTC is significantly different from the genetic signature seen in other forms of thyroid cancer. We performed a comprehensive literature review on the association between the molecular features of HTC and cancer metabolism. We searched the Pubmed, Embase, and Medline databases for clinical and translational studies published between 1980 and 2020 in English, coupling “HTC” with the following keywords: “genomic analysis”, “mutations”, “exome sequencing”, “molecular”, “mitochondria”, “metabolism”, “oxidative phosphorylation”, “glycolysis”, “oxidative stress”, “reactive oxygen species”, and “oncogenes”. HTC is characterized by frequent complex I mitochondrial DNA mutations as early clonal events. This genetic signature is associated with the abundance of malfunctioning mitochondria in cancer cells. HTC relies predominantly on aerobic glycolysis as a source of energy production, as oxidative phosphorylation-related genes are downregulated. The enhanced glucose utilization by HTC is used for diagnostic purposes in the clinical setting for the detection of metastases by fluorodeoxyglucose positron emission tomography (FGD-PET/CT) imaging. A comprehensive metabolomic profiling of HTC in association with its molecular landscape might be necessary for the implementation of tumor-specific therapeutic approaches. View Full-Text
Keywords: mitochondria; metabolism; Hürthle cell; oxidative phosphorylation; thyroid cancer; oncogenes mitochondria; metabolism; Hürthle cell; oxidative phosphorylation; thyroid cancer; oncogenes
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Kumari, S.; Adewale, R.; Klubo-Gwiezdzinska, J. The Molecular Landscape of Hürthle Cell Thyroid Cancer Is Associated with Altered Mitochondrial Function—A Comprehensive Review. Cells 2020, 9, 1570.

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