Somatic Mutation of in Four Cases of Sporadic Cardiac Myxoma.

Background: Inactivating mutations of the protein kinase A regulatory subunit 1 alpha () gene have been reported in familial cardiac myxoma. However, the role of mutation in sporadic cardiac myxoma remains unknown.

Methods: Targeted next-generation sequencing (NGS) was performed to identify mutations with the gene in seven cases of sporadic cardiac myxomas. Sanger sequencing of DNA from cardiac myxoma specimens and matched peripheral blood samples was performed to verify the identified mutations.

Results: Targeted NGS of myxoma DNA revealed 232 single nucleotide variants in 141 genes and 38 insertion-deletion mutations in 13 genes. Six mutations were identified in four of the seven cardiac myxoma cases, and thus, the inactivating mutation rate was 57.2% (4/7, 95% CI=0.44-0.58, <0.05). The variants identified by Sanger sequencing analysis were consistent with those from the NGS analysis for the four myxoma specimens. All of the pathogenic mutations led to premature termination of , except for one synonymous mutation. Moreover, none of the nonsense and missense mutations found in the myxoma specimens were found in the matched peripheral blood samples.

Conclusion: Pathogenic mutations of the gene were identified in tumor specimens from four cases of sporadic cardiac myxoma, and the absence of these mutations in peripheral blood samples demonstrated that they were somatic mutations.