Objectives: Cardiac sarcomas are rare and the pathogenesis of this disease is widely unknown. In some sarcomas mutations have been found and highlighted the pathogenetic role of the genetic alterations underlying this disease. In this contribution we summarize clinical data from our center and present a selected case which was analyzed for epigenetic alterations by studying DNA methylation of cytosine guanine dinucleotides which is a key epigenetic modification affecting gene transcription and genome integrity.
Methods: Between May 1991 and May 2014, a total of 24 patients underwent surgical treatment of a primary cardiac sarcoma in our center. Pivotal analysis was performed on a patient aged 63 at the time of diagnosis of a hemangiosarcoma of the right atrium. Epigenetic analysis was performed after obtaining genomic DNA from the cardiac tumor of this patient. Sequencing of probes was performed by standard methods. BiSeq software was used for studying differential methylation of genomic regions. Cardiac muscle obtained from the left ventricular apex of patients with congestive heart failure served as controls (n = 4 patients).
Results: The mean survival of our cardiac sarcoma patients was 47 months, with dependency on the resection status (R0-resection: mean survival 64.7 months, R1/R2-resection: 6.1 months). This included surgical treatment as well as adjuvant therapy comprising radiation and/or chemotherapy on the basis of individual decision. One patient (63-years old) with a survival of more than 4 years by now received combined radiochemotherapy after in toto resection of a right atrial hemangiosarcoma of 10x7x5 cm. Epigenetic analysis of this tumor tissue clustered with tissue of a cardiac metastasis of pleomorphic sarcoma revealed differential methylation of 345 gene regions including 46 promoter regions compared with controls. Of pivotal interest appeared the alteration in methylation of genes such as nuclear receptor binding SET domain protein 1 (NSD1), Rhotekin or FSCN2.
Conclusion: Cardiac sarcoma remains a detrimental disease with often poor prognosis. Based on its rare occurrence, there are no treatment guidelines nor is there a deeper understanding of pathophysiologic mechanisms. Our epigenetic findings such as the alteration of mediators of Rho signaling to activate NF-kappa-B or of transcriptional regulators such as NSD1 may help to improve the understanding and treatment of cardiac sarcoma, which will be subject to further analysis.
