Abstract 4252: CCNE1 amplification in high-grade serous ovarian cancer: analysis of the GENIE database

Abstract

Abstract Background: High-grade serous ovarian cancer (HGSOC) is the most common histological subtype of ovarian cancer as well as the most lethal. A primary oncogenic driver in a subset of HGSOC patients, CCNE1 amplification is associated with poorer outcomes and resistance to standard treatment. This study aims to investigate the copy number gain of CCNE1 and the genetic mutations associated with CCNE1 amplification using a large cohort of clinico-genomic data. Methods: We queried the American Association of Cancer Research-Genomics Evidence Neoplasia Information Exchange (GENIE) registry database v12.1 for patients with HGSOC. We studied CCNE1 amplification and the clinical, demographic, and genetic mutation associations. Results: A total of 3297 HGSOC samples were extracted from the registry. The mean age of patients at sequencing was 62 ± 10 years. Out of 2416 samples profiled for copy number alterations, CCNE1 amplification was found in 13.6%, being the most commonly amplified gene, followed by AGO2 (11.7%) and MYC (9.7%). Co-amplification between CCNE1 and AKT2 was demonstrated. Between the 397 samples with CCNE1 amplification and 2088 without, the genes that were more frequently mutated in the CCNE1 amplified group were AKT2 (20.4% vs 3.2%, p<0.001), KRAS (11.3% vs 4.3%, p<0.001), BRD4 (8.0% vs 4.4%, p = 0.006), and ERBB2 (7.9% vs 4.0%, p = 0.003). Other genes were less frequently mutated in the CCNE1 amplified cohort such as NF1 (7.6 % vs 12.9%, p = 0.009), BRCA1 (3.7% vs 10.0%, p<0.001), BRCA2 (2.7% vs 7.4%, p = 0.003), RB1 (2.7% vs 6.4%, p = 0.013), and PTEN (1.2% vs 4.0%, p = 0.02). Frequencies of MYC, PIK3CA, KMT2D, CDK12, and TSC2 mutations were similar between the two groups. TP53 was mutated in 100% of samples. There were no significant differences between the two groups in primary race or total mutation count, and mean age at sequencing was similar. Conclusion: Somatic sequencing is warranted to identify patients of this subset of HGSOC, and understanding the co-amplifications and co-mutations is essential so that they are targeted for optimal survival outcomes. Citation Format: Ashaar Al-Akhras, Shaden Tashtoush, Alina Ghazou. CCNE1 amplification in high-grade serous ovarian cancer: analysis of the GENIE database. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4252.