Colorectal cancer (CRC) represents the most common cancer affecting Saudi males and the third most common among females. Several studies have also shown that CRC affecting Saudi population tends to be more aggressive and presents at an advanced stage. Patients with distant metastasis tend to have a particularly poor prognosis. The complex process of metastasis is being unravelled with the use of next generation sequencing. The genomic landscape and pattern of tumor evolution from CRC to distant metastasis have not been well elucidated in the Saudi population.

In this study, multi-region whole-exome sequencing (WES) will be performed on CRC primary tumors and their metastases (wherever available) from patients to understand the tumor evolution and metastatic dissemination of CRC. The resulting catalog of variants will be analyzed to explore evolutionary histories and compare the repertoire of events between the primary tumor and its corresponding metastasis. We aim to analyze the genomic DNA sequences of 200 primary CRC and the corresponding DNA from the cases that have developed distant metastases. With the goal of better understanding the pathobiology of colorectal carcinogenesis, we will use state of the art "deep sequencing" technology to decipher the molecular and genetic signature of Saudi CRC. 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 CRC. Our objectives will be achieved through the following aims:

1. the generation of comprehensive catalogues of genomic abnormalities (somatic mutations) in colorectal cancer.

2. for the catalogue for each colorectal cancer 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 models for tumor evolution and metastatic progression in colorectal cancer from Aims 1 and 2.

The outcome of this study will provide a better understanding of CRC 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 CRC patients.