Ovarian cancer and the evolution of subtype classifications using transcriptional profiling†

Abstract

Ovarian cancer is a complex disease with multiple subtypes, each having distinct histopathologies and variable responses to treatment. This review highlights the technological milestones and the studies that have applied them to change our definitions of ovarian cancer. Over the past 50 years, technologies such as microarrays and next-generation sequencing have led to the discovery of molecular alterations that define each of the ovarian cancer subtypes and has enabled further subclassification of the most common subtype, high-grade serous ovarian cancer (HGSOC). Improvements in mutational profiling have provided valuable insight, such as the ubiquity of TP53 mutations in HGSOC tumors. However, the information derived from these technological advances has also revealed the immense heterogeneity of this disease, from variation between patients to compositional differences within single masses. In looking forward, the emerging technologies for single-cell and spatially resolved transcriptomics will allow us to better understand the cellular composition and structure of tumors and how these contribute to the molecular subtypes. Attempts to incorporate the complexities ovarian cancer has resulted in increasing sophistication of model systems, and the increased precision in molecular profiling of ovarian cancers has already led to the introduction of inhibitors of poly (ADP-ribose) polymerases as a new class of treatments for ovarian cancer with DNA repair deficiencies. Future endeavors to define increasingly accurate classification strategies for ovarian cancer subtypes will allow for confident prediction of disease progression and provide important insight into potentially targetable molecular mechanisms specific to each subtype.

Keywords: animal models; microarray; ovarian cancer; single-cell RNA sequencing; subtype; transcription.