Key result
Loss of the 17q22-24 region and inactivating mutations in the PRKAR1A gene were frequently found in sporadic thyroid carcinomas but not benign adenomas, indicating its role as a tumor-suppressor.
Observational
PRKAR1A acts as a tumor-suppressor gene in sporadic thyroid cancer, with its inactivation or loss associated with malignant progression.
Answers are grounded in this paper and cite their sources.
May aid differentiation of malignant from benign thyroid nodules; supports PRKAR1A tumor-suppressor role but remains hypothesis-generating.
The tumor-suppressor gene encoding the cyclic AMP-dependent protein kinase A type I-alpha regulatory subunit PRKAR1A has been mapped to chromosome 17 (17q22-24) and is mutated in Carney complex, a familial neoplasia syndrome that is associated with thyroid tumors. Other genes implicated in cyclic nucleotide-dependent signaling have been investigated in thyroid tumorigenesis. We studied protein kinase A (PKA) activity in noninherited follicular thyroid adenomas and follicular, papillary, and undifferentiated (anaplastic) thyroid carcinomas. We then examined these and additional thyroid tumors for losses of the 17q22-24 PRKAR1A region, mutations of the PRKAR1A gene, and expression of its peptide product. Total PKA activity was markedly increased in carcinomas over that in adenomas, whereas the ratio of free vs. total PKA activity was decreased in cancer. Consistent with these findings, the 17q22-24 region was frequently lost in cancer but not in benign adenomas. A novel inactivating mutation of the PRKAR1A gene (leading to premature termination of the predicted protein) was found in an aggressive thyroid cancer. The tumor with PRKAR1A gene mutation, as well as the tumors with 17q allelic losses, showed decreased PRKAR1A expression by immunostaining. We conclude that PRKAR1A, the most abundant regulatory subunit of protein kinase A and a principal cyclic AMP-signaling modulator, acts as a tumor-suppressor gene in sporadic thyroid cancer. Published 2002 Wiley-Liss, Inc.
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Sandrini et al. (2002) conducted an observational in Sporadic thyroid cancer. PRKAR1A mutations and 17q22-24 allelic losses vs. Benign adenomas was evaluated on PKA activity, 17q22-24 loss, PRKAR1A mutations, and PRKAR1A expression. Loss of the 17q22-24 region and inactivating mutations in the PRKAR1A gene were frequently found in sporadic thyroid carcinomas but not benign adenomas, indicating its role as a tumor-suppressor.
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