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

The colonic adenoma-carcinoma sequence is a well-established model that describes the progression from benign adenomatous polyps to colorectal cancer. This sequence involves various genetic alterations that facilitate this transformation.

The first significant event in this sequence is typically the mutation in the APC (adenomatous polyposis coli) gene, which serves as a tumor suppressor. Loss of function of the APC gene results in the formation of benign polyps or adenomas in the colon. The progression of these adenomas to malignancy often involves additional mutations.

One of the critical drivers of the transition from adenoma to carcinoma is the mutation in the K-RAS oncogene. K-RAS mutations are common in colorectal cancer and are associated with the activation of several signaling pathways that promote cell proliferation and survival.

Another important alteration is the mutation of the p53 gene, which is also a tumor suppressor. Changes in p53 activity often occur later in the sequence and are associated with the progression and aggressiveness of the cancer.

The inclusion of c-myc in this sequence connects to its role in driving cell division and promoting oncogenic processes, making the combination of these four components—APC, c-myc, K-RAS, and p53—key