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 <i>TP53</i> (NM_000546.5):c.532del p.(His178Thrfs*69) and <i>CHEK2</i> (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 <i>TP53</i> allele in the tumor, consistent with a second hit, while it was the variant <i>CHEK2</i> allele that was lost in the tumor. Our data indicate that the germline <i>TP53</i> PV acts as a driver of tumorigenesis in the reported case and support a complex interaction between the germline <i>TP53</i> and <i>CHEK2</i> PVs. This case highlights the dynamic interplays of genetic alterations in tumorigenesis and emphasizes the need for continued investigation into the complex interactions between <i>TP53</i> and <i>CHEK2</i> PVs and into the association of undifferentiated embryonal sarcoma of the liver and Li-Fraumeni syndrome.