Classical PLAG1 break-apart signals were detected in 35.7% of sporadic cardiac myxomas, suggesting PLAG1 rearrangement may be an oncogenic driver in a subset of these tumors.
Case-Control (n=29)
No
PLAG1 rearrangement is present in a subset of sporadic cardiac myxomas, suggesting it may act as an oncogenic driver in these benign neoplasms.
Absolute Event Rate: 35.7% vs 13.3%
p-value: p=0.017
Background Sporadic cardiac myxoma (SCM) is the most common primary tumor of the heart; however, its molecular pathogenesis remains poorly understood. Unlike the familial forms associated with the Carney complex (CNC), SCM lacks well-defined genetic alterations. Recognizing the established role of pleomorphic adenoma gene 1 (PLAG1) rearrangements in developmental syndromes with cardiac anomalies and in neoplasms characterized by prominent myxoid stroma, we investigated whether similar genetic events occur in SCM. In parallel, we evaluated MYC amplification, considering its known association with the malignant transformation in the mesenchymal tumors. Methods We retrospectively analyzed 14 SCM cases using fluorescence in situ hybridization (FISH) to assess PLAG1 rearrangement and MYC amplification. Histological and immunohistochemical analyses were performed. Fifteen normal salivary gland tissues were used as controls for the FISH-based cutoff definition. The statistical tests included the ROC curve with AUC and Youden index, t-test, Welch's test, F -test, along with corrections using the Bonferroni and Benjamini–Hochberg methods. Results Classical PLAG1 break-apart signals were detected in 35.7% (5/14) of the SCMs. Atypical isolated 5′ (red) and 3′ (green) signals were frequently observed (64.3% and 85.7%, respectively), potentially reflecting unbalanced translocations or copy number variation. No MYC amplification was observed in any of the cases. Statistical analysis positively supported a 0.5% threshold for PLAG1 Break-Apart (PLAG1-BA). The histological features were consistent with typical SCM morphology, and there was no evidence of malignancy. Conclusion This study reveals PLAG1 rearrangement in a subset of SCMs, suggesting potential molecular similarities with other tumors characterized by an abundant myxoid stroma. The absence of MYC amplification reinforces the benign nature of these neoplasms. These findings raise new hypotheses regarding the pathogenesis of SCM and warrant further investigation into cardiac myxoid tumors.
Maffini et al. (Wed,) conducted a case-control in Sporadic cardiac myxoma (n=29). PLAG1 rearrangement vs. Normal salivary gland tissues was evaluated on PLAG1 rearrangement (break-apart signals >0.5%) (p=0.017). Classical PLAG1 break-apart signals were detected in 35.7% of sporadic cardiac myxomas, suggesting PLAG1 rearrangement may be an oncogenic driver in a subset of these tumors.