A pilot study comparing the genetic molecular biology of gestational and non-gestational choriocarcinoma.

Non-gestational choriocarcinoma (NGC) is a rare subtype of choriocarcinoma differing in origin and phenotypic characteristics compared to gestational choriocarcinoma (GC). This study aimed to analyze the molecular biology of GC and NGC and evaluate genetic anomalies of choriocarcinoma subtypes. DNA was extracted and paired from tumor-normal tissue of one NGC and one GC (control) patient for whole-exome sequencing. To further understand the role of , a regulator mutated in the NGC tumor, on upregulation in choriocarcinoma, CRISPR/Cas9 was used to induce site-specific mutations in choriocarcinoma cells JEG-3. We hypothesized that dysfunction would result in overexpression. Sequencing revealed the GC tumor contained > 7 times more somatic mutations than the NGC tumor. Missense (98.86% vs. 94.97%), stop-gain (0.57% vs. 0.93%), and frameshift mutations (0.57% vs. 4.10%) were observed in the GC and NGC samples, respectively ( = 24.63, < 0.00001). The transition substitution rate was 67.54% and 55.71% in the GC and NGC samples, while the transversion substitution rate was 32.46% and 44.29% in the GC and NGC samples, respectively ( = 11.56, < 0.000673). Pathway enrichment analysis revealed ECM-receptor interaction and graft-versus-host disease were most enriched in the GC and NGC tumors, respectively. investigations showed that mRNA and protein levels were downregulated in Cas9--sgRNA transfected cells compared to the control ( < 0.001), while protein levels were upregulated. Our findings display the genetic distinctness of choriocarcinoma subtypes, especially NGC, and further highlight the relationship between and in choriocarcinoma cells, laying the foundation for further investigations.