Role of TP53 Gene Mutations in the Pathogenesis of Colorectal Carcinoma
Keywords:Molecular pathogenesis, p53 oncogene, tumor suppressor gene, colorectal cancer, tp53 mutations, oncogenesis
Colorectal cancer (CRC) is the third most commonly diagnosed cancer in both men and women in the world. The underlying molecular mechanisms that drive colorectal carcinogenesis are not fully known. However, P53 gene mutation, the most reported somatic mutation, is observed in about 50% of colorectal cancer patients.
Colorectal carcinoma is multifactorial. TP53 gene, the most novel tumor suppressor gene, acts as a major gatekeeper by preserving the genetic composition of a cell and prevents the oncogenic transformation of a cell. MDM2 and CUL-4A belong to the E3 ubiquitin ligase family, blocks P53 activation, and thus act as an oncogene. TRIM67 also has defective ligase activity, and its mutation is seen in about 80% of colorectal carcinomas. miRNA inhibits the tumor suppressor effect of TP53 and downstream signaling pathways, resulting in carcinogenesis. K RAS, WT1, IGF-1 are other markers of colorectal carcinoma. P53 antibodies produce by colorectal carcinomatous tissue are the markers used for screening and diagnosis.
P53 mutation drives a phenomenon of colorectal tumorigenesis. It serves as a biomarker, a prognostic factor, and a therapeutic target of colorectal carcinoma. Further studies are strongly recommended to improve the therapeutic approach of colorectal carcinoma.