| Autor: |
Kuhlen M; Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Augsburg, 86156 Augsburg, Germany., Schaller T; Pathology, Faculty of Medicine, University of Augsburg, 86156 Augsburg, Germany., Dintner S; Pathology, Faculty of Medicine, University of Augsburg, 86156 Augsburg, Germany., Stadler N; Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Augsburg, 86156 Augsburg, Germany., Hofmann TG; Institute of Toxicology, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany., Schmutz M; Hematology and Oncology, Faculty of Medicine, University of Augsburg, 86156 Augsburg, Germany., Claus R; Pathology, Faculty of Medicine, University of Augsburg, 86156 Augsburg, Germany.; Comprehensive Cancer Center Augsburg, Faculty of Medicine, University of Augsburg, 86156 Augsburg, Germany., Frühwald MC; Pediatrics and Adolescent Medicine, Faculty of Medicine, University of Augsburg, 86156 Augsburg, Germany., Golas MM; Human Genetics, Faculty of Medicine, University of Augsburg, 86156 Augsburg, Germany. |
| Abstrakt: |
Undifferentiated embryonal sarcoma of the liver is a rare mesenchymal malignancy that predominantly occurs in children. The relationship between this tumor entity and germline pathogenic variants (PVs) remains undefined. Here, we present the clinical case of a male patient diagnosed with undifferentiated embryonal sarcoma of the liver. Both germline and tumor samples were analyzed using next-generation sequencing. In the tumor tissue, PVs in TP53 (NM_000546.5):c.532del p.(His178Thrfs*69) and CHEK2 (NM_007194.4):c.85C>T p.(Gln29*) were identified, with both confirmed to be of germline origin. Copy number analyses indicated a loss of the wildtype TP53 allele in the tumor, consistent with a second hit, while it was the variant CHEK2 allele that was lost in the tumor. Our data indicate that the germline TP53 PV acts as a driver of tumorigenesis in the reported case and support a complex interaction between the germline TP53 and CHEK2 PVs. This case highlights the dynamic interplays of genetic alterations in tumorigenesis and emphasizes the need for continued investigation into the complex interactions between TP53 and CHEK2 PVs and into the association of undifferentiated embryonal sarcoma of the liver and Li-Fraumeni syndrome. |
