In Saudi Arabia, ovarian cancer (OC) is the seventh most common cancer and accounts for approximately 2.9% of all female cancers. High-grade serous ovarian carcinoma (HGSOC) is the most frequent type of ovarian carcinoma with a poor clinical outcome; patients with metastasis have dismal survival. The complex process of metastasis is becoming more understandable with the use of Next-Generation Sequencing. The genomic landscape and pattern of tumor evolution from HGSOC to distant metastasis have not been elucidated. In this study, multi-region whole-exome sequencing (WES) will be performed on HGSOC primary tumors and their metastases (wherever available) from patients to understand the tumor evolution and metastatic dissemination of HGSOC tumors. The resulting catalog of variants will be analyzed to explore evolutionary histories and compare the repertoire of events between primary and metastasis.

We aim to analyze the genomic DNA sequences of 100 primary ovarian cancers and the corresponding DNA from the cases that have developed metastases. With the goal of a better understanding of the pathobiology of ovarian carcinogenesis, we will use state-of-the-art "deep sequencing" technology to decipher the molecular and genetic signature of Saudi ovarian cancer. The development of next-generation (NextGen) sequencing technologies has spurred high hopes for the identification of novel biomarkers for disease diagnosis, prognosis, and prediction, including ovarian cancer. Our objectives will be achieved through the following aims:

1. the generation of comprehensive catalogues of genomic abnormalities (somatic mutations) in ovarian cancer of the epithelial ovarian cancer histology subtype.

2. for the catalogue of each epithelial ovarian cancer (EOC) to include the full range of somatic mutations, including single-nucleotide variants, insertions, deletions, copy number changes, translocations and other chromosomal rearrangements.

3. to generate a model for tumor evolution and metastatic progression in epithelial ovarian cancer from Aims 1 and 2.

The outcome of this study will provide a better understanding of EOC and should have important clinical implications, as it could result in the development of new and better strategies for targeted therapeutic intervention for the treatment of Saudi Arabian EOC tumors.