Rabbit Anti-Human CCNE1 (Phospho-Thr77) polyclonal antibody

Purpose of review The most common type of ovarian cancer, high-grade serous ovarian carcinoma (HGSOC), was originally thought to develop from the ovarian surface epithelium. However, recent data suggest that the cells that undergo neoplastic transformation and give rise to the majority of HGSOC are from the fallopian tube. This development has impacted both translational research and clinical practice, revealing new opportunities for early detection, prevention, and treatment of ovarian cancer. Recent findings Genomic studies indicate that approximately 50% of HGSOC are characterized by mutations in genes involved in the homologous recombination pathway of DNA repair, especially BRCA1 and BRCA2. Clinical trials have demonstrated successful treatment of homologous recombination-defective cancers with poly-ribose polymerase inhibitors through synthetic lethality. Recently, amplification of CCNE1 was found to be another major factor in HGSOC tumorigenesis, accounting for approximately 20% of all cases. Interestingly, amplification of CCNE1 and mutation of homologous recombination repair genes are mutually exclusive in HGSOC. Summary The fallopian tube secretory cell is the cell of origin for the majority of ovarian cancers. Although it remains unclear what triggers neoplastic transformation of these cells, certain tumors exhibit loss of BRCA function or amplification of CCNE1. These alterations represent unique therapeutic opportunities in ovarian cancer.

The treatment of epithelial ovarian cancer (EOC) is narrowly focused despite the heterogeneity of this disease in which outcomes remain poor. To stratify EOC patients for targeted therapy, we developed an approach integrating expression and genomic analyses including the BRCAness status. Gene expression and genomic profiling were used to identify genes recurrently (>5%) amplified and overexpressed in 105 EOC. The LST (Large-scale State Transition) genomic signature of BRCAness was applied to define molecular subgroups of EOC. Amplified/overexpressed genes clustered mainly in 3q, 8q, 19p and 19q. These changes were generally found mutually exclusive. In the 85 patients for which the genomic signature could be determined, genomic BRCAness was found in 52 cases (61.1%) and non-BRCAness in 33 (38.8%). A striking mutual exclusivity was observed between BRCAness and amplification/overexpression data. Whereas 3q and 8q alterations were preferentially observed in BRCAness EOC, most alterations on chromosome 19 were in non-BRCAness cases. CCNE1 (19q12) and BRD4 (19p13.1) amplification/overexpression was found in 19/33 (57.5%) of non-BRCAness cases. Such disequilibrium was also found in the TCGA EOC data set used for validation. Potential target genes are frequently amplified/overexpressed in non-BRCAness EOC. We report that BRD4, already identified as a target in several tumor models, is a new potential target in high grade non-BRCAness ovarian carcinoma.