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Precision Oncology of High-Grade Ovarian Cancer Defined through Targeted Sequencing
Sandra Wessman1, Beatriz Bohorquez Fuentes1, Therese Törngren2
1Department of Oncology-Pathology, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
Background:
We examined whether molecular characterization of high-grade epithelial ovarian cancer can inform the diagnosis and/or identify potential actionable targets.
Methods:
All of the consecutively sequenced high-grade ovarian tumours with consent between 2014 until 2019 were included. A total of 274 tumours underwent next generation sequencing using a targeted panel.
Results:
Patients with high-grade ovarian epithelial cancer were consented to prospective molecular characterization. Clinical information was extracted from their medical record. Tumour DNA was subjected to sequencing, and selected patients received PARP inhibitor therapy.
Conclusions:
Tumours from 274 women were sequenced, including high-grade serous carcinoma (n = 252), clear cell carcinoma (n = 4), carcinosarcoma (n = 9), endometrioid carcinoma (n = 3), undifferentiated carcinoma (n = 1), and mixed tumours (n = 5). Genomic profiling did not influence histologic diagnosis. Mutations were identified in TP53, BRCA1, BRCA2, as well as additional homologous recombination repair pathway genes BARD1, ATR, CHEK2, PALB2, RAD51D, RAD50, SLX4, FANCA, RAD51C, and RAD54L. In addition, mutations in PTEN and CDKN2A were identified. Several somatic mutations with implications for germline testing were identified, including RMI1, STK11, and CDH1. Germline testing identified 16 previously unknown BRCA1/2 carriers. Finally, 20 patients were treated with the PARP inhibitor olaparib based on the sequencing results.
Insights
Molecular characterization of high-grade ovarian cancer identified actionable targets and new BRCA1/2 carriers. Genomic profiling guided PARP inhibitor therapy in 20 patients, improving treatment strategies.
Area of Science:
- Oncology
- Genomics
- Molecular Diagnostics
Background:
- High-grade epithelial ovarian cancer (HGEOC) diagnosis can be challenging.
- Molecular characterization may reveal actionable targets for HGEOC treatment.
Purpose of the Study:
- To assess if molecular characterization of HGEOC can aid diagnosis.
- To identify potential actionable therapeutic targets in HGEOC.
Main Methods:
- 274 HGEOC tumors underwent next-generation sequencing (NGS) using a targeted panel.
- Clinical data was extracted from patient medical records.
- Selected patients received PARP inhibitor therapy based on sequencing results.
Main Results:
- Genomic profiling did not alter the initial histologic diagnosis.
- Mutations were identified in key genes including TP53, BRCA1, BRCA2, and other homologous recombination repair (HRR) pathway genes.
- Somatic mutations with germline testing implications were found, leading to the identification of 16 new BRCA1/2 carriers.
Conclusions:
- Molecular characterization of HGEOC identified numerous mutations in cancer-related genes.
- Genomic profiling identified actionable targets, leading to PARP inhibitor treatment in 20 patients.
- This approach can uncover germline mutations and guide targeted therapy selection.
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