Otolaryngology Department lab identifies novel gene mutation in familial thyroid cancer

Dr. Darrin Bann, an otolaryngology resident atPenn State Health Milton S. Hershey Medical CenterandPenn State College of Medicine, with the Otolaryngology research team, identified a novel gene mutation in familial non-medullary thyroid cancers. The mutation is the only familial thyroid cancer-associated mutation identified in a gene that is predominantly expressed in thyroid tissue.

Thyroid cancer is the most common endocrine malignancy in the United States, with more than 62,000 diagnoses in 2015. There is a high degree of heritability in thyroid cancer compared to other cancers, with first degree relatives having a 5.5-fold increase in relative risk of disease. Thestudy，发表在最近的癌症研究中，开发了研究家族性非甲状腺甲状腺癌的遗传原因。

宾夕法尼亚州立医学院医学院/博士医学科学家培训计划的校友班恩（Bann）与高级研究人员合作Dr. David Goldenberg, chair of the Department of Otolaryngology – Head and Neck Surgery at the Milton S. Hershey Medical Center and the College of Medicine, and詹姆斯·布拉奇, chair of the Department of Biochemistry and Molecular Biology and director of theInstitute for Personalized Medicine at Penn State College of Medicine.

The research team studied a family where thyroid cancer occurred in eight people across four generations. Using next generation sequencing, they were able to identify a mutation in a gene called DUOX2. This gene carries instructions for producing an enzyme called dual oxidase 2, which is involved in the production of hydrogen peroxide in the thyroid gland.

Through a series of biochemical analyses, the researchers found that dual oxidase 2 was still functional, despite being mutated. They determined that the mutated form of the enzyme was producing more hydrogen peroxide than the wildtype enzyme.

Taking their findings a step further, the investigators tested whether dual oxidase 2 expression was also dysregulated in sporadic thyroid cancer. By genotyping 64 individuals with sporadic non-medullary thyroid cancer, they determined that there was an association between an individual having the rs965513 thyroid cancer risk polymorphism and increased expression of the DUOX2 gene.

班恩指出，这提供了有力的证据，表明过氧化氢的失调是发展甲状腺癌的遗传易感性的可能机制。这一发现可能具有显着的翻译意义，包括确定防止过量氧化氢产生的氧化损伤的潜力。

“If we can identify a series of common mutations that increase oxidative damage in those who are at risk, we could potentially mitigate some of the risk by treating those patients with antioxidants,” Bann said.

这项研究的结果是，研究人员有很多机会扩展其发现。该突变本身对于开发用于研究零星甲状腺癌的动物模型可能是有用的，该模型可能对甲状腺癌发展的机制有了新的启示，或者有助于鉴定治疗靶标。班恩说，必须测试其他非医学甲状腺癌的人和家庭，以查看他们是否具有DUOX2的基因突变。

Other investigators from Penn State College of Medicine include Kathryn Sheldon, Kenneth Houser, Lan Nguyen,Joshua WarrickandMaria Baker.

坦普尔大学刘易斯·卡茨医学院的昆扬·金和格伦·格哈德也为这项研究做出了贡献。

This work was supported, in part, by a grant with the Pennsylvania Department of Health using Tobacco CURE funds to Dr. David Goldenberg.