Molecular profiling of gestational trophoblastic neoplasia: Identifying therapeutic targets

Leah McNally, Sharon Wu, Kurt Hodges, Matt Oberley, John J. Wallbillich, Nathaniel L. Jones, Thomas J. Herzog, Premal H. Thaker, Angeles Alvarez Secord, Marilyn Huang

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: The treatment for high risk or recurrent gestational trophoblastic neoplasia (GTN) is a highly toxic multi-agent chemotherapy. For patients with progressive or recurrent GTN, checkpoint inhibitors have demonstrated anti-tumor activity; however, identification of novel therapies for GTN remain an unmet need. Therefore, we sought to characterize the molecular landscape of GTN to identify potential therapeutic targets. Methods: GTN samples were analyzed using a combination of molecular – next-generation sequencing (NGS) or whole exome sequencing (WES)- and protein- Immunohistochemistry (IHC) analyses. GTN samples encompassed complete moles, choriocarcinoma, epithelioid trophoblastic tumors (ETT), and placental site trophoblastic tumors (PSTT). Results: We analyzed 30 cases of GTN including 15 choriocarcinoma, 7 ETT, 5 PSTT, 1 invasive mole and 2 mixed histologies. The median age was 41.5. GTN samples were found to be PD-L1 positive (92.3%), tumor mutational burden (TMB) low (92.8%), and microsatellite stable (MSS) (100%). Forty-six percent of choriocarcinoma specimens contained a genomic alteration including TP53 (33%) and homologous recombination repair (HRR) (13%) genes. Alterations in RTK-RAS pathway signaling was present in 40% of ETT cases. Conclusions: The high rate of PD-L1 positivity in this real-world database and reported in prior literature support continued clinical trial development evaluating immunotherapy for treatment of GTN. Other potential targeted treatments identified include Wee1, PARP and MEK inhibitors based on molecular alterations in TP53, HRR genes, and RTK-RAS pathways respectively.

Original languageEnglish
Pages (from-to)111-116
Number of pages6
JournalGynecologic oncology
Volume184
DOIs
StatePublished - May 2024

Keywords

  • Choriocarcinoma
  • ETT
  • Gestational trophoblastic neoplasia
  • Molecular profiling
  • PD-L1
  • PSTT

Fingerprint

Dive into the research topics of 'Molecular profiling of gestational trophoblastic neoplasia: Identifying therapeutic targets'. Together they form a unique fingerprint.

Cite this