<unk>  can have different inheritance patterns and different genetic causes. When this condition results from mutations in the APC gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene is sufficient to cause the disorder. The incidence of malignancy in these cases approaches 100%. In most cases, an affected person has one parent with the condition. APC gene mutation variants The APC is a tumour suppressor gene responsible for the production of<unk>  polyposis coli (APC), a large multifunction tumour-suppressing protein which acts as a "gatekeeper" to prevent development of tumours. (APC regulates β-catenin, a protein that plays a crucial role in cell communication, signalling, growth, and controlled destruction, but which left uncontrolled also gives rise to numerous cancers). A flaw in the APC gene means APC is not as effective as it should be, and over time it is likely that some cells that should have been controlled by APC will not be, and will instead continue to develop and become cancerous. In<unk>  polyposis they usually manifest as polyps—small abnormalities on the surface of the intestinal tract. Although the polyps are inherently benign, the first step of the two-hit hypothesis has already taken place: the inherited APC mutation. Often, the remaining "normal" allele is mutated or deleted, accelerating generation of polyps. Further mutations (e.g., in p53 or kRAS) to APC-mutated cells are much more likely to lead to cancer than they would in non-mutated epithelial cells. The normal function of the APC gene product is still being investigated; it is present in both the cell nucleus and the membrane. The canonical tumor-suppressor function of APC is suppression of β-catenin, but other tumor-suppressor functions of APC may be related to cell adherence and cytoskeleton organization. Mutation of APC also occurs commonly in incident cases of colorectal carcinoma, emphasizing its importance in this form of cancer. MUTYH gene mutation variants MUTYH encodes DNA repair enzyme MYH glycosylase. During normal cellular activities, guanine sometimes becomes altered by oxygen, which causes it to pair with adenine instead of cytosine. MYH glycosylase fixes these mistakes by base excision repair, such that mutations do not accumulate in the DNA and lead to tumor formation. When MYH glycosylase does not function correctly, DNA errors may accrue to initiate tumorigenesis with a clinical presentation similar to that in patients with APC mutations. Mutations in the MUTYH gene are inherited in an autosomal recessive pattern, which means two copies of the gene must be altered for a person to be affected by the disorder. Most often, the parents of a child with an autosomal recessive disorder are not affected but are carriers of one copy of the altered gene. Animal models The "ApcMin" mouse model was described in 1990 and carries an Apc allele with a stop codon at position 850. Heterozygosity for this mutation results in a fully penetrant phenotype on most genetic backgrounds, with mice on a sensitive background developing over 100 tumors in the intestinal tract. The number and location of the intestinal tumors are modified by unlinked genes. Many other models have since appeared, including a model of attenuated<unk>  (the 1638N model) and several conditional mutants that allow for tissue-specific or temporal ablation of gene function. For more information see mouse models of colorectal and intestinal cancer. In 2007, the "ApcPirc" rat model was isolated with a stop codon at position 1137. In contrast to the mouse models where >90% of tumors form in the small intestine, the Pirc rat forms tumors preferentially (>60%) in the large intestine, similar to the human clinical presentation.
Familial adenomatous polyposis
Hereditary nonpolyposis colorectal cancer
Juvenile polyposis syndrome
MUTYH-associated polyposis
Serrated polyposis syndrome
Pseudopolyps
Ogden syndrome
Polymerase proofreading-associated polyposis