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PRKAR1A and Thyroid Tumors

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
Author to whom correspondence should be addressed.
Academic Editors: Fabio Medas and Pier Francesco Alesina
Cancers 2021, 13(15), 3834;
Received: 16 June 2021 / Revised: 24 July 2021 / Accepted: 27 July 2021 / Published: 30 July 2021
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment of Thyroid Carcinoma)
In 2021 it is estimated that there will be 44,280 new cases of thyroid cancer in the United States and the incidence rate is higher in women than in men by almost 3 times. Well-differentiated thyroid cancer is the most common subtype of thyroid cancer and includes follicular (FTC) and papillary (PTC) carcinomas. Over the last decade, researchers have been able to better understand the molecular mechanisms involved in thyroid carcinogenesis, identifying genes including but not limited to RAS, BRAF, PAX8/PPARγ chromosomal rearrangements and others, as well as several tumor genes involved in major signaling pathways regulating cell cycle, differentiation, growth, or proliferation. Patients with Carney complex (CNC) have increased incidence of thyroid tumors, including cancer, yet little is known about this association. CNC is a familial multiple neoplasia and lentiginosis syndrome cause by inactivating mutations in the PRKAR1A gene which encodes the regulatory subunit type 1α of protein kinase A. This work summarizes what we know today about PRKAR1A defects in humans and mice and their role in thyroid tumor development, as the first such review on this issue.
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 BRAF, RAS as well as RET/PTC and PAX8/PPARγ 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 (PRKAR1A) 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 Prkar1a can cause FTC. In this review, we provide an overview of the molecular mechanisms contributing to thyroid tumorigenesis associated with inactivation of the RRKAR1A gene. View Full-Text
Keywords: thyroid carcinoma; PRKAR1A; PKA; Carney complex; cAMP thyroid carcinoma; PRKAR1A; PKA; Carney complex; cAMP
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MDPI and ACS Style

Pitsava, G.; Stratakis, C.A.; Faucz, F.R. PRKAR1A and Thyroid Tumors. Cancers 2021, 13, 3834.

AMA Style

Pitsava G, Stratakis CA, Faucz FR. PRKAR1A and Thyroid Tumors. Cancers. 2021; 13(15):3834.

Chicago/Turabian Style

Pitsava, Georgia, Constantine A. Stratakis, and Fabio R. Faucz 2021. "PRKAR1A and Thyroid Tumors" Cancers 13, no. 15: 3834.

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