Activating mutation of PDGFRB gene in a rare cardiac undifferentiated intimal sarcoma of the left atrium: a case report.

Xiaoling Fu,Ji Li,Weixin Niu,Hikmat A Al-Ahmadie,Sizhi Paul Gao,Qi Li,Amber J Kiliti,Gopa Iyer

doi:10.18632/oncotarget.20700

Abstract

Cardiac sarcoma is a rare malignant tumor with undefined genetic mutations and no targeted therapy. Here in one rare case of undifferentiated cardiac intimal sarcoma (IS), a next-generation sequencing based assay, MSK-IMPACT (Memorial Sloan Kettering - Integrated Mutation Profiling of Actionable Cancer Targets), identified a somatic, activating mutation in PDGFRB, along with amplification of PDGFRA. This E472D mutation of PDGFRB was discovered for the first time in IS. These findings suggest that concurrent aberrant PDGFRA and PDGFRB signaling may be a diagnostic biomarker and molecular therapeutic target of IS of the heart.

Highlights

Primary malignant cardiac tumors are very rare, with an incidence of 0.001% ~ 0.003%, with sarcomas comprising 75%. [1]
These variants were subjected to lower requirements on coverage, number of mutant reads and variant frequency to be considered as high confidence calls
The overall prognosis of cardiac sarcomas (CS) is dismal, with surgical resection being the only effective treatment option, as Cardiac sarcomas (CS) does not respond to conventional radiation and chemotherapy

Summary

INTRODUCTION

Primary malignant cardiac tumors are very rare, with an incidence of 0.001% ~ 0.003% , with sarcomas comprising 75%. [1]. Each antibody has established high specificity for their protein target [6] This assay was chosen because: 1) Duolink has a high specificity for detection of pPDGFRB due to a dual recognition format, as shown previously [6]; 2) IHC and immunofluorescence staining using antibodies against pPDGFRB was low in sensitivity and specificity (data not shown) [6]; 3) we attained Duolink technology expertise as previously demonstrated [7]. Using this technique, we discovered pPDGFRB was present in the IS tumor section, but not in the normal control heart tissue (Figure 5) (Supplementary Figure 2)

MATERIALS AND METHODS

DISCUSSION

Findings

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