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Case report: whole exome sequencing of primary cardiac angiosarcoma highlights potential for targeted therapies
Leah Zhrebker1,2, Irene Cherni3, Lara M Gross4
1Baylor Charles A. Sammons Cancer Center at Dallas, Baylor University Medical Center at Dallas, 3410 Worth Street, Dallas, TX, 75246, USA. Leah.Zhrebker@BSWHealth.org.
Background:
Primary cardiac angiosarcomas are rare, but they are the most aggressive type of primary cardiac neoplasms. When patients do present, it is with advanced pulmonary and/or cardiac symptoms. Therefore, many times the correct diagnosis is not made at the time of initial presentation. These patients have metastatic disease and the vast majority of these patients die within a few months after diagnosis. Currently the treatment choices are limited and there are no targeted therapies available.
Case Presentation:
A 56-year-old male presented with shortness of breath, night sweats, and productive cough for a month. Workup revealed pericardial effusion and multiple bilateral pulmonary nodules suspicious for metastatic disease. Transthoracic echocardiogram showed a large pericardial effusion and a large mass in the base of the right atrium. Results of biopsy of bilateral lung nodules established a diagnosis of primary cardiac angiosarcoma. Aggressive pulmonary disease caused rapid deterioration; the patient went on hospice and subsequently died. Whole exome sequencing of the patient's postmortem tumor revealed a novel KDR (G681R) mutation, and focal high-level amplification at chromosome 1q encompassing MDM4, a negative regulator of TP53.
Conclusion:
Mutations in KDR have been reported previously in angiosarcomas. Previous studies also demonstrated that KDR mutants with constitutive KDR activation could be inhibited with specific KDR inhibitors in vitro. Thus, patients harboring activating KDR mutations could be candidates for treatment with KDR-specific inhibitors.
Insights
Primary cardiac angiosarcomas are aggressive neoplasms. A novel KDR mutation was identified in a patient, suggesting potential targeted therapy with KDR inhibitors for angiosarcoma.
Area of Science:
- Oncology
- Genetics
Background:
- Primary cardiac angiosarcomas are rare, aggressive neoplasms.
- Diagnosis is often delayed due to advanced symptoms.
- Limited treatment options and no targeted therapies exist.
Observation:
- A 56-year-old male presented with advanced cardiopulmonary symptoms.
- Diagnostic workup revealed pericardial effusion and pulmonary nodules.
- Postmortem tumor sequencing identified a novel KDR (G681R) mutation and MDM4 amplification.
Findings:
- The patient's angiosarcoma harbored a novel KDR mutation.
- KDR mutations have been previously associated with angiosarcomas.
- Activating KDR mutations can be targeted by specific inhibitors in vitro.
Implications:
- Patients with activating KDR mutations may benefit from KDR-specific inhibitors.
- This finding opens avenues for targeted therapy in cardiac angiosarcoma.
- Further research into KDR inhibitors for angiosarcoma is warranted.
