Cardiac sarcoma is a rare tumor. Currently, there is a lack of data on the genomic profiling in Chinese cardiac sarcoma patients. In this study, we analyzed the genomic alterations and prognostic biomarkers of this kind of patients.
Total FFPE samples of 26 cardiac sarcoma patients who received operation during 2010 to 2018 were enrolled in this study. FFPE samples from these patients were collected for WES (Whole Exome Sequencing). Genomic alterations including single base substitution, copy number variations, gene fusions and rearrangement were assessed. Tumor mutational burden (TMB) was also analyzed by NGS algorithm.
The cohort of 26 cardiac sarcoma patients included 13 males and 13 females with a median age of 54 (range 27-68). Patients were followed up for 8 years (10 patients) or until patients died (16 patients). The median overall survive (OS) was 14 months. This cohort included 18 angiosarcomas (AS), 6 intimal sarcomas (IS), 1 liposarcoma (LPS) and 1 synovial sarcoma (SS). The most commonly altered genes were KDR (35%), MDM2 (31%), FRS2 (27%), KMT2D (23%), CKD4 (23%), GLI1 (23%) and TERT (23%). Several druggable genomic alterations including amplification of CDK4 (6/26), KIT (5/26), KDR (2/26), PDGFRA (2/26), ERBB3 (1/26), and mutations of BRAF (1/26), BRCA1 (1/26) and PTEN (1/26) were found. AS patients with alterations of TP53, TRMT10C, ALMS1, CCDC157, CCNJL, KIAA2026 or OSBPL7 gene had a poor prognosis with a median OS of 3 months, while AS patients without alterations of any those genes had a median OS of 21 months. Interestingly, MDM2 amplification was only found in IS and LPS, but not in AS, which was confirmed by FISH analysis. The median TMB was 29 muts/Mb (2.3-56.5 muts/Mb) in this cohort.
Our study firstly revealed the genomic profiling of Chinese cardiac sarcoma patients. Several genes may be relevant with prognosis in AS, and MDM2 amplification may be a potential biomarker to distinguish between different subtypes. Most of the patients (92.3%) presented high TMB value which may potentially benefitted to immunotherapy. Due to limited number of patients, the correlation of gene mutations with clinical features need to be further analyzed.
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All authors have declared no conflicts of interest.