Which of the following are tumor suppressor genes that have been associated with the development of colorectal cancer?

a. The DCC gene

b. The APC gene

c. The P53 gene

Loss of specific chromosomal regions represent genetic alterations that are associated with the development of colorectal neoplasms in a high percentage of cases. These chromosomal regions have been hypothesized to contain tumor-suppressor genes whose products normally regulate growth and differentiation in a negative fashion. One such gene linked to familial adenomatous polyposis was mapped to the long arm of chromosome 5q and referred to as the APC (adenomatosis polyposis coli) gene. The gene codes for a 300 kilodalton protein which has recently been shown to bind to b-catenin, implying an important role in cell adhesion and possibly cytoskeleton function. It is hypothesized that disruption of cell adhesion and cytoskeleton function can lead to loss of contact inhibition which may promote neoplastic transformation as well as invasiveness of cancer cells.

Another tumor suppressor gene thought to be important in colorectal tumorigenesis is the p53 gene located in chromosome 17p. Alteration in p53 is one of the most common genetic events seen in human malignancies. The p53 gene produces a DNA-binding phosphoprotein that is important in cell proliferation, differentiation and cell survival. Allelic loss of p53 has been observed in more than 75% of colorectal carcinomas.

Another common genetic alteration associated with colorectal tumors is an allelic loss of chromosome 18q. This is where the "deleted in colorectal carcinoma" gene, also termed DCC is located. Mutations in DCC are present in 47% of late adenomas and 73% of carcinomas. The DCC protein shares significant homology with the neural cell adhesion molecule family that regulates cell adhesion and recognition.