Double Heterozygous Pathogenic Variants in TP53 and CHEK2 in Boy with Undifferentiated Embryonal Sarcoma of the Liver

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 (NM_000546.5):c.532del p.(His178Thrfs*69) and (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 allele in the tumor, consistent with a second hit, while it was the variant allele that was lost in the tumor. Our data indicate that the germline PV acts as a driver of tumorigenesis in the reported case and support a complex interaction between the germline and PVs. This case highlights the dynamic interplays of genetic alterations in tumorigenesis and emphasizes the need for continued investigation into the complex interactions between and PVs and into the association of undifferentiated embryonal sarcoma of the liver and Li-Fraumeni syndrome.