Here we report the disruption of the APC gene caused by somatic insertion of a long interspersed repetitive element (LINE-1 sequence) into the last exon of the APC gene in a colon cancer.
They imply that inactivation of APC, MCC, and/or a linked gene on chromosome 5q plays a role in the pathogenesis of some cancers of the upper gastrointestinal tract, as well as in colon cancer and familial adenomatous polyposis.
High-resolution banding studies indicated that the deletion in the patient with polyposis spans the region 5q21-q22, which includes APC, a gene involved in familial adenomatous polyposis and sporadic colon cancer.
The APC gene on chromosome 5 causing adenomatous polyposis coli represents a minority of the inherited colon cancer cases, while hereditary-non polyposis colon cancer (HNPCC) may cause five percent of all human colon cancer.
The APC gene is a putative human tumor-suppressor gene responsible for adenomatous polyposis coli (APC), an inherited, autosomal dominant predisposition to colon cancer.
The APC gene, mutations in which are responsible for the inherited colon cancer syndrome adenomatous polyposis coli (APC), is described as a tumor suppressor gene.
Mutations in the adenomatous polyposis coli gene (which encodes a protein called APC) are associated with the formation of intestinal polyps and colon cancers.
Defects in the APC gene are inarguably linked to the progression of colon cancers that arise both sporadically and through the transmission of germline mutations.
Therefore, this model may have some relevance and application to the study of colon cancer in human inflammatory bowel disease, which is not associated with APC mutations or with Ki-ras or p53 mutations.
In summary, we did not detect any functional mutations of the APC gene in a wide variety of tumors except for a colon cancer cell line, suggesting that alterations of the APC gene do not have a major role in the development of lung and renal cancers, various types of sarcomas, or hematological malignancies.
Peptide-mediated precipitation experiments showed that anti-APCp1 bound and sequestered wild-type and mutant APC proteins in extracts of human colon cancer cell lines.
Mutant forms of beta-catenin have been discovered in colon cancers that retain wild-type APC genes, and also in melanomas, medulloblastomas, prostate cancer and gastric and hepatocellular carcinomas.
We have shown that the family's phenotype does not result from APC mutations (including the I1307K variant) or from genetic changes in the other known genes that predispose to colon cancer.
Our findings suggest APC mutations alter regulation of both beta- and gamma-catenin, perhaps explaining why the frequency of APC mutations in colon cancer far exceeds that of beta-catenin mutations.
The reported association between the APCI1307K mutation and colon cancer risk was supported by a correlation in these data between personal or family history of CRC or polyps and a gene mutation.
The adenomatous polyposis coli (APC) gene was first identified as the gene mutated in an inherited syndrome of colon cancer predisposition known as familial adenomatous polyposis coli (FAP).
Inactivation of the tumor suppressor adenomatous polyposis coli (APC) protein is a critical early step in the development of familial and sporadic colon cancer.