부산대학교 도서관

Objectives: The molecular characterization of gestational trophoblastic neoplasia (GTN), a rare disease, has been limited by the lack of tumor specimens. Despite the recent use of immunotherapy, women with recurrent or chemo-resistant diseases have limited treatment options. Our objective was to describe the molecular landscape of GTNs and identify potential therapeutic targets. Methods: A total of 30 GTN tumor samples were analyzed using next-generation sequencing (NGS) or whole-exome sequencing (WES) and immunohistochemistry (IHC). PD-L1 IHC used SP-142 (cut-off ≥1%). MSI was tested by fragment analysis, IHC, and NGS. TMB was measured by totaling somatic mutations per tumor (high ≥10 mutations per MB). Statistical significance was determined by Chi-square and p-values adjusted for multiple comparisons (q) to be < 0.05. Results: Thirty cases of GTN consisted of 15 choriocarcinomas, three complete moles, seven epithelioid trophoblastic tumors (ETT), and five placental site trophoblastic tumors (PSTT) were included in the study. The median age was 41.5 years (range 26-69), and the majority (56.7%) were primary tumors. PD-L1 IHC was positive in 28/29 (96.6%) of cases while nearly all cases were TMB low (15/16, 93.8%) and microsatellite stable (MSS) (17/17, 100%). TP53 mutations were the most common, occurring in 33.3% of choriocarcinoma cases. Homologous recombination repair (HRR) pathway alterations were identified in 13.3% of choriocarcinoma cases. RTK-RAS pathway was altered in 2/5 (40%) ETT cases and 1/14 (7.1%) choriocarcinoma cases (Table 1). Conclusions: Data is consistent with previously published literature demonstrating high PDL1 expression across GTN subtypes, strongly supporting a role for checkpoint blockade. Potential alternate targeted therapies for recurrent or chemoresistant GTN include Wee1, PARP, MEK inhibitors targeting TP53 , HRR , and KRAS alterations. [ABSTRACT FROM AUTHOR]