What are key aspects of the colonic adenoma-carcinoma sequence?

The colonic adenoma-carcinoma sequence is a well-established model that describes the progression of colorectal cancer from benign lesions (adenomas) to malignant tumors (carcinomas). The correct answer highlights key genetic mutations and alterations involved in this process.

The involvement of APC (Adenomatous Polyposis Coli) is crucial, as it is one of the first mutations that can drive the development of adenomatous polyps. APC is a tumor suppressor gene, and its loss leads to the accumulation of β-catenin, promoting cell proliferation and survival, thereby initiating the adenoma formation.

Following the APC mutation, K RAS mutations are commonly observed and are associated with the progression of these adenomas into more advanced lesions. The presence of activated K RAS contributes to further dysregulation of cell signaling pathways, promoting malignant transformation.

Eventually, mutations in the p53 tumor suppressor gene often occur in later stages of tumor development. The loss of p53 function disables critical pathways that regulate the cell cycle and apoptosis, allowing for further evolution of the tumor.

This sequence illustrates a gradual accumulation of genetic alterations, starting with the initial APC mutation, followed by K RAS activation, and culminating with p53 mutations, ultimately leading to