DCC held a controversial place as a tumour suppressor gene for many years, and is well known as an axon guidance receptor that responds to netrin-1.

DCC was initially cloned out of the region and put forth as a putative tumour suppressor gene, though nothing was known about its function at the time.

Several years later DCC was shown to encode a transmembrane receptor protein that mediated the effects of netrin-1 on axon outgrowth.

A gradient of netrin-1 is produced from the floor plate, which allows orientation of the extending axons, aiding the development of the dorsal-ventral axis of the brain and spinal column.

DCC and netrin have been found to be specifically involved in the secondary migration of neural crest cells into the pancreas and developing gut structures, and may prove to be vital to other areas during fetal growth.

[23] One of the most frequent genetic abnormalities that occur in advanced colorectal cancer is loss of heterozygosity (LOH) of DCC in region 18q21.

DCC in a receptor for netrin-1 and is currently believed by some to be a conditional tumour suppressor gene, meaning that it normally prevents cell growth when in the absence of netrin-1.

[24] In the absence of ligand, DCC interacts with caspase-9 (likely via an unidentified adaptor protein) and promotes the assembly of a caspase-activating complex.

In a cancer state, the absence of DCC prevents the gradient from having an effect on the cell, making it more likely to continue to survive.

This type of instability is associated with some specific mutations, including genes involved with DNA mismatch repair and surprisingly, transforming growth factor-beta.

Many reviews refuse to comment on DCC due to its history of conflicting information, stating that more study is required.

This segment spans 7.64cM, which is a relatively large section of DNA that could easily encompass more than one tumour suppressor gene.

Studies found that more tumours had reduced DCC expression than could be explained by LOH or MSI, indicating that another mechanism was at work.

Loss of DCC in colorectal cancer primarily occurs via chromosomal instability, with only a small percent having epigenetic silencing involved.

Epigenetic silencing of DCC by promoter hypermethylation has shown to be a significant factor in other cancer types.

Currently the American Society of Clinical Oncology does not recommend using DCC as a marker due to insufficient classification data.

A recent review of over two dozen 18q LOH-survival studies concluded that there was a significant amount of inconsistency between the data sets.

They concluded that loss of 18q remains a marker for poor prognosis, and that DCC status has the potential to define a group of patients who may benefit from specific treatment regimes.

[29] The increase in loss of heterozygosity percentages of chromosome 18q21 have long suggested that DCC may be involved in the progression of benign adenomas to malignant carcinomas.

Recently it has been shown that a sensitizing treatment regimen of amphetamines causes markedly increased levels of DCC and UNC-5 expression on neuron cell bodies.

Although DCC has been studied for many years, a significant amount of the data collected is contradictory and much of the focus has been on getting clear picture of the basics.

When the genetic abnormalities that occur in advanced colorectal cancer were first identified, one of the most frequent events was found to be loss of heterozygosity (LOH) of region 18q21.

The fact that DCC heterozygotes had no increased rates of cancer, even when crossed with mice carrying Apc mutations, solidified this viewpoint.

They found an increase in apoptosis that corresponded to DCC expression, which was completely eliminated when netrin-1 was co-transfected or simply added to the media.