Case report: whole exome sequencing of primary cardiac angiosarcoma highlights potential for targeted therapiesReport as inadecuate

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BMC Cancer

, 17:17

Genetics, genomics and epigenetics


BackgroundPrimary 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 presentationA 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.

ConclusionMutations 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.

KeywordsCardiac angiosarcoma Whole exome sequencing Activating gene mutation Targeted therapies AbbreviationsaCGHarray Comparative Genomic Hybridization

BAFB-allele frequencies

BWABurrows-Wheeler Aligner

CDCluster of differentiation

CDKN2ACyclin Dependent Kinase Inhibitor 2A


CNSCentral nervous system

CTAG1ACancer-Testis Antigen 1A

CTAG2Cancer-Testis Antigen 2

CTAsCancer testis antigens

CTSBCathepsin B

CUL3Cullin 3

DLRSDerivative log2ratio spread

ESPR1Epithelial Splicing Regulatory Protein 1

FFPEFormalin-Fixed, Paraffin-Embedded

FLT1Fms Related Tyrosine Kinase 1

FLT4Fms Related Tyrosine Kinase 4

GATA4GATA Binding Protein 4


INDELsInsertions and deletions

I-SET domainImmunoglobulin Suvar3-9, Enhancer-of-zeste, Trithorax

KDRKinase Insert Domain Receptor

KRASV-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog

LOHLoss of heterozygosity

MAGE-A1 – 2BMelanoma Antigen Family Member A1 – 2B

MAPKAPK2Mitogen-Activated Protein Kinase-Activated Protein Kinase 2

MDM2MDM2 oncogene, E3 ubiquitin protein ligase

MDM4MDM4 p53 binding protein homolog

MDMXAny MDM protein

MSAMultiple sequence alignment

MYCV-Myc Avian Myelocytomatosis Viral Oncogene Homolog

PIK3C2BPhosphatidylinositol-4-Phosphate 3-Kinase Catalytic Subunit Type 2 Beta

PLCG1Phospholipase C, gamma 1

PTPRBProtein tyrosine phosphatase, receptor type, B

SNRKSNF Related Kinase

SNVsSingle nucleotide variations

TEKTEK Receptor Tyrosine Kinase

TIE1Tyrosine Kinase with Immunoglobulin like and EGF Like Domains 1

TNKSTankyrase 1

TP53tumor protein P53

USP17L2Ubiquitin Specific Peptidase 17-Like Family Member 2

VEGFR2Vascular endothelial growth factor receptor 2


Electronic supplementary materialThe online version of this article doi:10.1186-s12885-016-3000-z contains supplementary material, which is available to authorized users.

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Author: Leah Zhrebker - Irene Cherni - Lara M. Gross - Margaret M. Hinshelwood - Merrick Reese - Jessica Aldrich - Joseph M. Gui


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