Frequent protein kinase A regulatory subunit A1 mutations but no GNAS mutations as potential driver in sporadic cardiac myxomas.

Autor: Zimpfer A; Institute of Pathology, University Medical Center Rostock, Strempelstr. 14, Rostock, 18055 Germany. Electronic address: annette.zimpfer@med.uni-rostock.de., Abel LM; Institute of Pathology, University Medical Center Rostock, Strempelstr. 14, Rostock, 18055 Germany., Alozie A; Department of Cardiac Surgery, Rostock Heart Center, University Medical Center Rostock, Schillingallee 35, 18057, Rostock, Germany., Etz CD; Department of Cardiac Surgery, Rostock Heart Center, University Medical Center Rostock, Schillingallee 35, 18057, Rostock, Germany., Schneider B; Institute of Pathology, University Medical Center Rostock, Strempelstr. 14, Rostock, 18055 Germany.
Jazyk: angličtina
Zdroj: Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology [Cardiovasc Pathol] 2024 Jul-Aug; Vol. 71, pp. 107632. Date of Electronic Publication: 2024 Mar 15.
DOI: 10.1016/j.carpath.2024.107632
Abstrakt: Purpose: Cardiac myxomas (CMs) are the second most common benign primary cardiac tumors, mainly originating within the left atrium. Approximately 5% of CM cases are associated with Carney Complex (CNC), an autosomal dominant multiple neoplasia syndrome often caused by germline mutations in the protein kinase A regulatory subunit 1A (PRKAR1A). Data concerning PRKAR1A alterations in sporadic myxomas are variable and sparse, with PRKAR1A mutations reported to range from 0% to 87%. Therefore, we investigated the frequency of PRKAR1A mutations in sporadic CM using next-generation sequencing (NGS). Additionally, we explored mutations in the catalytic domain of the Protein Kinase A complex (PRKACA) and examined the presence of GNAS mutations as another potential driver.
Methods and Results: This study retrospectively collected histological and clinical data from 27 patients with CM. First, we ruled out the possibility of underlying CNC through clinical evaluations and standardized interviews for each patient. Second, we performed PRKAR1A immunohistochemistry (IHC) analysis and graded the reactivity of myxoma cells semi-quantitatively. NGS was then applied to analyze the coding regions of PRKAR1A, PRKACA, and GNAS in all 27 cases. Of the 27 sporadic CM cases, 13 (48%) harbored mutations in PRKAR1A. Among these 13 mutant cases, six displayed more than one mutation in PRKAR1A. Most of the identified mutations resulted in premature stop codons or affected splicing. In PRKAR1A mutant CM cases, the loss of PRKAR1A protein expression was significantly more common. In two cases with missense mutations, protein expression remained preserved. Furthermore, a single mutation was detected in the catalytic domain of the protein kinase A complex, while no GNAS mutations were found.
Conclusion: We identified a relatively high frequency of PRKAR1A mutations in sporadic CM. These PRKAR1A mutations may also represent an important oncogenic mechanism in sporadic myxomas, as already known in CM cases associated with CNC.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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