The following is a summary of “Molecular Subclasses of Clear Cell Ovarian Carcinoma and Their Impact on Disease Behavior and Outcomes ” published in the November 2022 issue of Clinical Cancer by Bolton et al.

The goal of this study is to classify clear cell ovarian carcinoma (CCOC)  into molecular subtypes and evaluate how these subtypes affect clinical manifestation and patient outcomes. Using a targeted deep sequencing panel of 163 suspected CCOC driver genes, we sequenced the entire RNA genome of 211 tumors and characterized 421 primary CCOCs that had passed quality control. Clinical features and overall survival were evaluated in relation to molecularly determined categories.

Here, researchers report that 95% (401/421) of CCOC tumors harbor a potential somatic driver mutation in at least 1 candidate gene, with the most common mutations being found in ARID1A (49%), PIK3CA (49%), TERT (20%), and TP53 (16%). About 2 distinct CCOC subtypes emerged from the clustering of cancer driver mutations and RNA expression. Tumors harboring TP53 mutations were characterized by an enrichment for the expression of genes involved in an extracellular matrix organization and mesenchymal differentiation, while tumors harboring ARID1A mutations exhibited an enrichment for the expression of canonical CCOC genes and markers of platinum resistance. 

Women whose tumors carried the TP53 mutation were more likely to have an advanced illness at presentation, to have no history of endometriosis, and to have a poorer prognosis than those whose tumors included the ARID1A mutation. In addition, there was a tendency toward a decreased rate of response to first-line platinum-based therapy in women whose tumors carried the ARID1A mutation. Their results imply that CCOC can be divided into 2 molecular subclasses, each of which has its own unique clinical presentation and outcomes and may have bearing on how well patients respond to standard and novel treatments.