OA: Molecular Characterization of Epithelial Ovarian Cancer: Implications for Diagnosis and Treatment

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 Next-generation/high-throughput sequencing has been used to investigate tumor evolution of specimens of high-grade serous ovarian cancer [40,48,49,51,52,53], as well as non-serous ovarian cancer lesions [40].

 It is, however, clear that overcoming disease resistance to treatment will require a diversity of approaches. Furthermore, it is critically important that the putative drivers of individual tumors uncovered in molecular studies are linked with the discovery of new single-agent and combination targeted regimens in the setting of clinical trials, such as those targeting multiple therapeutic pathways based on the specific molecular characteristics of the disease in individual patients [142,143].

 (see chart below) Figure 2. (A) Histological subtypes of ovarian cancer; and (B) widely accepted epithelial ovarian cancer classification paradigm based on clinicopathologic and molecular evidence that type I and type II tumors develop through different pathways (Kurman et al. [18]). * Indicates rare tumor; ^† Mucinous and malignant Brenner tumors are considered to be possible exceptions that may arise from transitional cells at or close to the junction of the fallopian tube and the peritoneum.

 
Abstract

Epithelial ovarian cancer is a highly heterogeneous disease characterized by multiple histological subtypes. Molecular diversity has been shown to occur within specific histological subtypes of epithelial ovarian cancer, between different tumors of an individual patient, as well as within individual tumors. Recent advances in the molecular characterization of epithelial ovarian cancer tumors have provided the basis for a simplified classification scheme in which these cancers are classified as either type I or type II tumors, and these two categories have implications regarding disease pathogenesis and prognosis. Molecular analyses, primarily based on next-generation sequencing, otherwise known as high-throughput sequencing, are allowing for further refinement of ovarian cancer classification, facilitating the elucidation of the site(s) of precursor lesions of high-grade serous ovarian cancer, and providing insight into the processes of clonal selection and evolution that may be associated with development of chemoresistance. Potential therapeutic targets have been identified from recent molecular profiling studies of these tumors, and the effectiveness and safety of a number of specific targeted therapies have been evaluated or are currently being studied for the treatment of women with this disease.

 

 Table 1. Type I ovarian cancers: Frequencies of selected potentially pathogenic genomic alterations.

 

Table 2. Selected genomic alterations and their frequencies in high-grade serous ovarian carcinoma from the TCGA ^a.