The Second Allele: A Key to Understanding the Timing of Sporadic and Hereditary Colorectal Tumorigenesis

Our understanding of the molecular basis of colorectal neoplasia is derived from Mendelian genetics, with tumor suppressor genes contributing more to the deregulation of growth than oncogenes. In patients with hereditary syndromes, expression of one allele of a key tumor suppressor gene is absent at birth. The loss of the expression of the second allele precipitates tumorigenesis. However, there are multiple ways in which the expression of the second allele of a tumor suppressor gene is lost. Here, we review these ways and their possible effect on phenotype.