TY - JOUR
T1 - Molecular profiling of gestational trophoblastic neoplasia
T2 - Identifying therapeutic targets
AU - McNally, Leah
AU - Wu, Sharon
AU - Hodges, Kurt
AU - Oberley, Matt
AU - Wallbillich, John J.
AU - Jones, Nathaniel L.
AU - Herzog, Thomas J.
AU - Thaker, Premal H.
AU - Secord, Angeles Alvarez
AU - Huang, Marilyn
N1 - Publisher Copyright:
© 2024
PY - 2024/5
Y1 - 2024/5
N2 - 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.
AB - 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.
KW - Choriocarcinoma
KW - ETT
KW - Gestational trophoblastic neoplasia
KW - Molecular profiling
KW - PD-L1
KW - PSTT
UR - http://www.scopus.com/inward/record.url?scp=85184050011&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2024.01.033
DO - 10.1016/j.ygyno.2024.01.033
M3 - Article
C2 - 38301309
AN - SCOPUS:85184050011
SN - 0090-8258
VL - 184
SP - 111
EP - 116
JO - Gynecologic oncology
JF - Gynecologic oncology
ER -