Abstract 1649: Large scale multi-omics concordance study of cyclin E1 identifies high expressing tumors lacking CCNE1 gene alterations across multiple tumor indications

Abstract Cyclin E1 is a key regulator of the G1/S transition and is thought to cause excessive entry into the cell cycle. CCNE1 is amplified in a range of tumor indications, and its amplification is associated with poorer prognosis and resistance to chemotherapy. Cyclin E1 is also being investigated as a potential biomarker for inhibitors targeting the replication stress response. Understanding the best way to quantify cyclin E1 overexpression is fundamental to support patient selection approaches for these inhibitors. In many cases, gene amplification correlates with increased cyclin E1 protein expression; however, there are a proportion of high-grade serous ovarian cancer and basal-like breast cancer cases where cyclin E1 protein overexpression does not correlate with gene amplification. In this study, we investigate if this phenomenon is observed in other cancers and some of the potential mechanisms causing cyclin E1 overexpression. We used a multi-omics approach to assess cyclin E1 expression in 1417 formalin-fixed paraffin-embedded (FFPE) patient tumor resections across 6 indications (SCCHN, Bladder, NSCLC, TNBC, Ovarian 2, 17% cases had high CCNE1 mRNA and 29% had high cyclin E1 protein (H-score ≥100). 15. 7% (130/830) cases had high protein expression without gene amplification or gain, crucially this was found across all 6 indications (n=20/102 SCCHN, n=29/166 Bladder, n=34/232 NSCLC, n=15/76 SCLC, n=15/143 TNBC Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 1649.