Molecular basis for stool-based DNA tests for colorectal cancer: a primer for clinicians

Cancers develop as a result of alterations in genes that regulate growth, survival, and other cellular behaviors. Colorectal cancers develop through one of at least three different pathways, termed chromosomal instability, microsatellite instability, and the CpG island methylator phenotype. Although there is some overlap, these pathways tend to inactivate different sets of tumor suppressor genes and tend to have somewhat different biological behaviors. Tumor cells and DNA are shed into the fecal stream, and uniquely mutated genes can be identified that would indicate the likely presence of a neoplasm in the gastrointestinal tract. By understanding the pathways to tumor development, the target genes involved, and the mechanisms underlying genomic instability, it will be possible to implement strategies to detect and treat the different types of colorectal cancer.