Pitsava Georgia, Stratakis Constantine A, Faucz Fabio R
Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Cancers (Basel). 2021 Jul 30;13(15):3834. doi: 10.3390/cancers13153834.
Thyroid cancer is the most common type of endocrine malignancy and the incidence is rapidly increasing. Follicular (FTC) and papillary thyroid (PTC) carcinomas comprise the well-differentiated subtype and they are the two most common thyroid carcinomas. Multiple molecular genetic and epigenetic alterations have been identified in various types of thyroid tumors over the years. Point mutations in , as well as and chromosomal rearrangements are common. Thyroid cancer, including both FTC and PTC, has been observed in patients with Carney Complex (CNC), a syndrome that is inherited in an autosomal dominant manner and predisposes to various tumors. CNC is caused by inactivating mutations in the tumor-suppressor gene encoding the cyclic AMP (cAMP)-dependent protein kinase A (PKA) type 1α regulatory subunit () mapped in chromosome 17 (17q22-24). Growth of the thyroid is driven by the TSH/cAMP/PKA signaling pathway and it has been shown in mouse models that PKA activation through genetic ablation of the regulatory subunit can cause FTC. In this review, we provide an overview of the molecular mechanisms contributing to thyroid tumorigenesis associated with inactivation of the gene.
甲状腺癌是最常见的内分泌恶性肿瘤，其发病率正在迅速上升。滤泡状甲状腺癌（FTC）和乳头状甲状腺癌（PTC）构成了分化良好的亚型，它们是两种最常见的甲状腺癌。多年来，在各种类型的甲状腺肿瘤中已发现多种分子遗传和表观遗传改变。 中的点突变以及 和 染色体重排很常见。在卡尼综合征（CNC）患者中已观察到甲状腺癌，包括FTC和PTC，CNC是一种以常染色体显性方式遗传且易患各种肿瘤的综合征。CNC是由位于17号染色体（17q22 - 24）上的编码环磷酸腺苷（cAMP）依赖性蛋白激酶A（PKA）1α型调节亚基（ ）的肿瘤抑制基因的失活突变引起的。甲状腺的生长由促甲状腺激素（TSH）/ cAMP / PKA信号通路驱动，并且在小鼠模型中已表明，通过调节亚基 的基因消融激活PKA可导致FTC。在本综述中，我们概述了与 基因失活相关的甲状腺肿瘤发生的分子机制。
