Genetic Variants Implicate Dual Oxidase-2 in Familial and Sporadic Nonmedullary Thyroid Cancer
| Autor: | Glenn S. Gerhard, Kathryn Sheldon, Darrin V. Bann, Qunyan Jin, David M. Goldenberg, Lan K. Nguyen, Maria J. Baker, Kenneth R. Houser, James R. Broach, Joshua I. Warrick |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Cancer Research Familial Nonmedullary Thyroid Cancer medicine.disease_cause Germline Cell Line 03 medical and health sciences 0302 clinical medicine Chlorocebus aethiops medicine Animals Humans Genetic Predisposition to Disease Amino Acid Sequence Thyroid Neoplasms Thyroid cancer Mutation Polymorphism Genetic Hydrogen peroxide metabolism business.industry Thyroid Genetic variants Dual oxidase 2 Middle Aged medicine.disease Dual Oxidases 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis COS Cells Cancer research Female business Sequence Alignment |
| Zdroj: | Cancer Research. 79:5490-5499 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Highly penetrant hereditary thyroid cancer manifests as familial nonmedullary thyroid cancer (FNMTC), whereas low-penetrance hereditary thyroid cancer manifests as sporadic disease and is associated with common polymorphisms, including rs965513[A]. Whole-exome sequencing of an FNMTC kindred identified a novel Y1203H germline dual oxidase-2 (DUOX2) mutation. DUOX2Y1203H is enzymatically active, with increased production of reactive oxygen species. Furthermore, patients with sporadic thyroid cancer homozygous for rs965513[A] demonstrated higher DUOX2 expression than heterozygous rs965513[A/G] or homozygous rs965513[A]-negative patients. These data suggest that dysregulated hydrogen peroxide metabolism is a common mechanism by which high- and low-penetrance genetic factors increase thyroid cancer risk. Significance: This study provides novel insights into the genetic and molecular mechanisms underlying familial and sporadic thyroid cancers. |
| Databáze: | OpenAIRE |
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