Case report: whole exome sequencing of primary cardiac angiosarcoma highlights potential for targeted therapies

Abstract 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\u2019s 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

Additional file 2: Table S2. of Case report: whole exome sequencing of primary cardiac angiosarcoma highlights potential for targeted therapies

Basic Next Generation Sequencing Whole Exome Alignment Statistics. (DOCX 13 kb

Additional file 3: Figure S1. of Case report: whole exome sequencing of primary cardiac angiosarcoma highlights potential for targeted therapies

Genome-wide chromosomal copy number plot outputs from 1A) copy number analysis, 1B) LOH and allelic imbalance analysis, 1C) segmentation algorithm copy number analysis, and 1D) ExomeCNV copy number analysis. 1A) chromosomal plots contain chromosomal map position in megabases on the X-axis, and the log2 fold change ratio information on the Y-axis. Regions of copy neutrality (ratios between log2FC -0.75 and +0.75) are black, regions of copy number gain (ratio > log2FC 0.75) are red, and regions of copy number loss (ratios < log2FC -0.75) are green. 1B) chromosomal plots contain chromosomal map position in megabases on the X-axis, and the B-allele frequency (BAF) on the Y-axis revealing chromosomal allelic imbalances. 1C) the copy number log2 fold change ratios (Y-axis) for each chromosome are colored alternately in green and black across the entirety of the genome map positions along the X-axis. 1D) chromosomal plots contain chromosomal map position in megabases on the X-axis, and the log2 fold change ratio information on the Y-axis derived from ExomeCNV. (ZIP 7726 kb