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 ( = 252), clear cell carcinoma ( = 4), carcinosarcoma ( = 9), endometrioid carcinoma ( = 3), undifferentiated carcinoma ( = 1), and mixed tumours ( = 5). Genomic profiling did not influence histologic diagnosis. Mutations were identified in , , , as well as additional homologous recombination repair pathway genes , , , , , , , , , and . In addition, mutations in and were identified. Several somatic mutations with implications for germline testing were identified, including , , and . Germline testing identified 16 previously unknown BRCA1/2 carriers. Finally, 20 patients were treated with the PARP inhibitor olaparib based on the sequencing results.
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http://dx.doi.org/10.3390/cancers13205240 | DOI Listing |
Cancer Med
January 2025
Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.
Background: Borderline ovarian tumors (BOTs) differ from ovarian carcinomas in their clinical presentation and behavior, yet their molecular characteristics remain poorly understood. This study aims to address this gap by integrating whole-exome sequencing (WES) and RNA sequencing (RNA-seq) to compare BOTs with high-grade serous carcinoma (HGSC), endometrioid carcinoma (EC), and clear-cell carcinoma (CCC).
Objective: To elucidate the molecular features of BOTs and evaluate their similarities and differences in comparison to HGSC, EC, and CCC.
Clin Cancer Res
January 2025
Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
Purpose: Mesothelin (MSLN) is highly expressed in high grade serous/ endometrioid ovarian cancers (HGOC). Anetumab ravtansine (AR) is an antibody drug conjugate directed at MSLN antigen with a tubulin polymerization inhibitor. We assessed safety, activity and pharmacokinetics of the combination AR/bevacizumab (Bev) (ARB) versus weekly paclitaxel (wP)/Bev (PB) in patients with platinum resistant/refractory HGOC (prrHGOC).
View Article and Find Full Text PDFCancer Res Commun
January 2025
Indiana University School of Medicine, Bloomington, IN, United States.
Ovarian cancer is a deadly gynecological disease with frequent recurrence. Current treatments for patients include platinum-based therapy regimens with PARP inhibitors specific for HR-deficient high-grade serous ovarian cancers (HGSOCs). Despite initial effectiveness, patients inevitably develop disease progression as tumor cells acquire resistance.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, T2N 2T9, Canada.
Intratumoral heterogeneity (ITH) is spatial, phenotypic, or molecular differences within the same tumor that have important implications for accurate tumor classification and assessment of predictive biomarkers. The Canadian Ovarian Experimental Unified Resource (COEUR) has created a cohort of 437 FFPE tissue specimens from 108 tubo-ovarian high-grade serous carcinoma (HGSC) patients to quantify ITH across the anatomical sites and between primary and recurrence. We quantified the ITH of six clinically used immunohistochemical diagnostic and prognostic biomarkers (WT1, p53, p16, PR, CD8, and Ki67).
View Article and Find Full Text PDFPrz Menopauzalny
December 2024
Department of Surgical and Endoscopic Gynecology, Medical University of Lodz, Lodz, Poland.
Introduction: Ovarian cancer is a significant cause of death among females. MiRNAs, particularly the miR-196 family, can influence tumor progression by targeting specific pathways. Detecting ovarian cancer early is challenging, highlighting the need for additional biomarkers such as miRNAs to improve diagnosis and treatment strategies.
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