Genomic Characterization of Rare Primary Cardiac Sarcoma Entities

Primary cardiac sarcomas are considered rare malignant entities associated with poor prognosis. In fact, knowledge regarding their gene signature and possible treatments is still limited. In our study, whole-transcriptome sequencing on formalin-fixed paraffin-embedded (FFPE) samples from one cardiac osteosarcoma and one cardiac leiomyosarcoma was performed, to investigate their mutational profiles and to highlight differences and/or similarities to other cardiac histotypes. Both cases have been deeply detailed from a pathological point of view. The osteosarcoma sample presented mutations involving ATRX, ERCC5, and COL1A1, while the leiomyosarcoma case showed EXT2, DNM2, and PSIP1 alterations. Altered genes, along with the most differentially expressed genes in the leiomyosarcoma or osteosarcoma sample versus the cardiac angiosarcomas and intimal sarcomas (e.g., YAF2, PAK5, and CRABP1), appeared to be associated with cell growth, proliferation, apoptosis, and the repair of DNA damage, which are key mechanisms involved in tumorigenesis. Moreover, a distinct gene expression profile was detected in the osteosarcoma sample when compared to other cardiac sarcomas. For instance, WIF1, a marker of osteoblastic differentiation, was upregulated in our bone tumor. These findings pave the way for further studies on these entities, in order to identify targeted therapies and, therefore, improve patients' prognoses.

Automated summary

Primary cardiac sarcomas are rare malignant tumors with poor prognosis. This study aimed to investigate the gene mutations and expression profiles of two types of cardiac sarcomas, osteosarcoma and leiomyosarcoma, using whole-transcriptome sequencing. The results revealed specific genetic alterations and differential gene expression in these two types of sarcomas compared to other cardiac histotypes, which could be associated with tumorigenesis mechanisms. These findings provide insights for further research on targeted therapies and improving the prognosis of patients with primary cardiac sarcomas.