title: Case report: whole exome sequencing of primary cardiac angiosarcoma highlights potential for targeted therapies.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Baylor Charles A. Sammons Cancer Center at Dallas, Baylor University Medical Center at Dallas, 3410 Worth Street, Dallas, TX, 75246, USA. Leah.Zhrebker@BSWHealth.org.|Department of Internal Medicine, Baylor University Medical Center at Dallas, 3500 Gaston Ave, Dallas, TX, 75246, USA. Leah.Zhrebker@BSWHealth.org.
authors.forename: Leah
authors.initials: L
authors.lastname: Zhrebker
authors.affiliation: Integrative Cancer Genomics, Translational Genomics Research Institute, 445N 5th Street, Phoenix, AZ, 85004, USA.
authors.forename: Irene
authors.initials: I
authors.lastname: Cherni
authors.affiliation: Department of Internal Medicine, Baylor University Medical Center at Dallas, 3500 Gaston Ave, Dallas, TX, 75246, USA.
authors.forename: Lara M
authors.initials: LM
authors.lastname: Gross
authors.affiliation: Baylor Charles A. Sammons Cancer Center at Dallas, Baylor University Medical Center at Dallas, 3410 Worth Street, Dallas, TX, 75246, USA.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Hinshelwood
authors.affiliation: Baylor Charles A. Sammons Cancer Center at Dallas, Baylor University Medical Center at Dallas, 3410 Worth Street, Dallas, TX, 75246, USA.|Texas Oncology/US Oncology, 3410 Worth Street, Dallas, TX, 75246, USA.
authors.forename: Merrick
authors.initials: M
authors.lastname: Reese
authors.affiliation: Integrative Cancer Genomics, Translational Genomics Research Institute, 445N 5th Street, Phoenix, AZ, 85004, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Aldrich
authors.affiliation: Anatomic Pathology and Clinical Pathology, Baylor University Medical Center at Dallas, 3600 Gaston Ave, Dallas, TX, 75246, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Guileyardo
authors.affiliation: Department of Internal Medicine, Baylor University Medical Center at Dallas, 3500 Gaston Ave, Dallas, TX, 75246, USA.|Anatomic Pathology and Clinical Pathology, Baylor University Medical Center at Dallas, 3600 Gaston Ave, Dallas, TX, 75246, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Roberts
authors.affiliation: Integrative Cancer Genomics, Translational Genomics Research Institute, 445N 5th Street, Phoenix, AZ, 85004, USA.
authors.forename: David
authors.initials: D
authors.lastname: Craig
authors.affiliation: Clinical Translational Research Division Translational Genomics Research Institute, 445N 5th Street, Phoenix, AZ, 85004, USA.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Von Hoff
authors.affiliation: Baylor Charles A. Sammons Cancer Center at Dallas, Baylor University Medical Center at Dallas, 3410 Worth Street, Dallas, TX, 75246, USA.|Texas Oncology/US Oncology, 3410 Worth Street, Dallas, TX, 75246, USA.|College of Medicine, Texas A&M Health Sciences Center, 3410 Worth Street, Dallas, TX, 75246, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Mennel
authors.affiliation: Integrative Cancer Genomics, Translational Genomics Research Institute, 445N 5th Street, Phoenix, AZ, 85004, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Carpten
mesh_terms: D018797:Cell Cycle Proteins; D004252:DNA Mutational Analysis; D059472:Exome / Q000235:genetics; D017809:Fatal Outcome; D005784:Gene Amplification; D006338:Heart Neoplasms / Q000235:genetics*; D006394:Hemangiosarcoma / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; C482775:MDM4 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Activating gene mutation; Cardiac angiosarcoma; Targeted therapies; Whole exome sequencing