Thesis (M.Sc.) - Cairo University - Faculty of Science - Department of Zoology

Colorectal cancer (CRC) is a disease originating from the epithelial cells lining the colon or rectum of the gastrointestinal tract. In most CRC cases, the DNA mutations that lead to cancer are acquired during a person's life rather than having been inherited.There are certain risk factors that probably play a role in causing these acquired mutations, but so far most of them are not known. The functions of the major colon cancer genes have been reasonably well characterized. The most commonly mutated gene in all CRC is the Adenomatous Polyposis Coli (APC) gene, which produces the APC protein; it stops the accumulation of Ý-catenin protein. The p53 protein, produced by the TP53 gene, it normally controls a check point in cell division. TP53 gene mutations can transform an adenoma into an invasive carcinoma. Some genes in CRC that encoding the proteins KRAS, NRAS, B-RAF, and PI3K, can acquire mutations that result in over-activation of cell proliferation which constitutively stimulate the cell to divide. PTEN, a tumor suppressor gene, it normally inhibits PI3K, but can sometimes become mutated and deactivated. c-MET gene when overexpressed it is associated with greater tumor size in primary CRC, and also it is an important predictive marker for early-stage invasion and metastasis. Most pathogenic mutations in this major genes lead to a higher risk of disease, and environmental contributions are often difficult to recognize. We investigated these major genes and their correlation using the advanced technique Next generation sequencing (NGS). This is the first study to report hotspot mutations, genes overlapping and mutations co-occurrence in potential biomarkers using NGS in CRC patients in Egypt.Thus, this study can provide insights for developing targeted therapies with enhanced effect and help in optimizing personalized cancer therapy

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