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Cell Death Discov. 2018 Jul 23;4:18. doi: 10.1038/s41420-018-0072-3. eCollection 2018.

Combined effects of FH (E404D) and ACOX2 (R409H) cause metabolic defects in primary cardiac malignant tumor.

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1Institute of Reproduction and Development at Obstetrics & Gynecology Hospital, State Key Laboratory of Genetic Engineering at School of Life Sciences, Fudan University, Shanghai, China.
6Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Pathology, MD Andersen Cancer Center, Houston, TX USA.
3Dell Pediatric Research Institute, Department of Pediatrics, The University of Texas at Austin Dell Medical School, Austin, TX USA.
Shanghai Biotechnology Corporation, 121 Libing Road, Shanghai, China.
Institute of Cardiovascular Disease, General Hospital of Jinan Military Region, Jinan, China.
Contributed equally


Primary malignant cardiac tumors (PMCTs) are extremely rare. The apparent immunity of the heart to invasive cancer has attracted considerable interest given the continuously rising incidence of cancer in other organs. This study aims to determine the conditions that could result in cardiac carcinoma and expand our understanding of cardiac tumor occurrence. We report two cases: a male (Patient-1) with primary cardiac malignant fibrous histiocytoma (MFH) and a female (Patient-2) with primary cardiac angiosarcoma. Merged genome-wide analyses of aCGH, Exome sequencing, and RNA-sequencing were performed on Patient-1 using peripheral blood, carcinoma tissue, and samples of adjacent normal tissue. Only whole-transcriptome analysis was carried out on Patient-2, due to insufficient quantities of sample from Patient-2. We identified a novel inherited loss of functional mutation of FH (Glu404Asp), a recurrent somatic hotspot mutation of PIK3CA (His1047Arg) and a somatic duplication in copy number of HIF1A. FH (E404D) severely compromised FH enzyme activity and lead to decreased protein expression in cardiac tumor tissues. We previously reported a functional mutation ACOX2 (R409H), which is potentially associated with decreased β-oxidation of fatty acids in the cardiac tumor tissue. Results of transcriptome analyses on two patients further revealed that the RNA expression of genes in the TCA cycle and beta-oxidation were uniformly downregulated. In this study, combined effects of FH (E404D) and ACOX2 (R409H) on metabolic switch from fatty acids to glucose were remarkably distinct, which might be an essential precondition to trigger the occurrence of PMCTs and mimic the Warburg effect, a hallmark of cancer metabolism.

Conflict of interest statement

The authors declare that they have no conflict of interest.

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