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Published on: July 25, 2020
Molecular Characterization of Ovarian Yolk Sac Tumor (OYST)
Khalil Hodroj1, Aleksandra Stevovic2, Valery Attignon1
1Centre Léon Berard (CLB), 69008 Lyon, France.
Abstract:
Most patients with malignant ovarian germ cell tumors (MOGTCs) have a very good prognosis and chemotherapy provides curative treatment; however, patients with yolk sac tumors (OYSTs) have a significantly worse prognosis. OYSTs are rare tumors and promising results are expected with the use of specific therapeutic strategies after the failure of platinum-based first-line and salvage regimens. We initiated a project in collaboration with EORTC SPECTA, to explore the molecular characteristics of OYSTs. The pilot project used retrospective samples from ten OYST relapsed and disease-free patients. Each patient had a molecular analysis performed with FoundationOne CDx describing the following variables according to the Foundation Medicine Incorporation (FMI): alteration type (SNV, deletion), actionable gene alteration, therapies approved in EU (for patient's tumor type and other tumor types), tumor mutational burden (TMB), and microsatellite instability (MSI) status. A total of 10 patients with OYST diagnosed between 2007 and 2017 had a molecular analysis. A molecular alteration was identified in four patients (40%). A subset of three patients (33.3% of all patients) harbored targetable oncogenic mutations in KRAS, KIT, ARID1A. Two patients at relapse harbored a targetable mutation. This retrospective study identifies clinically relevant molecular alterations for all relapsed patients with molecular analysis. Dedicated studies are needed to demonstrate the efficacy of specific therapeutic strategies after the failure of platinum-based first-line and salvage regimens and to explore the potential relationship of a molecular alteration and patient outcome.
Insights
Molecular analysis of ovarian yolk sac tumors (OYSTs) identified actionable mutations in 40% of patients. Three patients (33.3%) had targetable oncogenic mutations, suggesting potential for new therapeutic strategies in relapsed OYSTs.
Area of Science:
- Oncology
- Genomics
- Molecular Diagnostics
Background:
- Malignant ovarian germ cell tumors (MOGTCs) generally have a good prognosis, but ovarian yolk sac tumors (OYSTs) present a worse outcome.
- Effective therapeutic strategies for relapsed OYSTs after standard treatments are needed.
Purpose of the Study:
- To explore the molecular characteristics of ovarian yolk sac tumors (OYSTs).
- To identify actionable gene alterations in relapsed OYST patients.
Main Methods:
- Retrospective analysis of molecular data from ten relapsed and disease-free OYST patients.
- FoundationOne CDx comprehensive genomic profiling was performed.
- Analysis included alteration type, actionable gene alterations, approved therapies, tumor mutational burden (TMB), and microsatellite instability (MSI) status.
Main Results:
- Molecular alterations were identified in 40% of the ten analyzed OYST patients.
- Three patients (33.3%) harbored targetable oncogenic mutations, including in KRAS, KIT, and ARID1A.
- Two patients at relapse presented with a targetable mutation.
Conclusions:
- This pilot study identified clinically relevant molecular alterations in relapsed OYST patients.
- Further dedicated studies are required to validate these findings and explore targeted therapies.
- Investigating the relationship between molecular alterations and patient outcomes is crucial.
