Germline mutations in the adenomatous polyposis coli (APC) gene cause familial adenomatous polyposis (FAP), an autosomal dominant disease characterized by hundreds to thousands of adenomatous polyps in the colon and rectum, with progression to colorectal cancer.
This last mutation occurs in the EB1-binding domain of the APC protein and segregates in four relatives of the patient with three of them presenting 2-3 adenomatous polyps.
Desmoid tumors are usually a complication of familial adenomatous polyposis, a predisposition to the early development of premalignant adenomatous polyps in the colorectum due to chain-terminating mutations of the APC gene.
Among the genetic defects associated with CRC, the APCI1307K mutation has been detected nearly exclusively in individuals of Ashkenazi Jewish (AJ) origin, occurring in 6%-7% of the AJ general population and in 10%-28% of AJ with a either a personal or family history of CRC or adenomatous polyps.
Germline mutations (nonsense, frameshift) of APC are associated with familial adenomatous polyposis, an autosomal dominant syndrome, clinically characterized by young onset, hundreds of adenomatous polyps in the colon, and increased risk for extracolonic tumors.
In this study, we have confirmed and refined the LOH-associated region in colorectal FAP: allelic loss in adenomatous polyps tended to occur when the germline mutation lay in the region of the APC gene between the first and second beta-catenin degradation repeats (codons 1285-1378).
Furthermore, the adenomatous polyposis coli (APC) gene on Chr 5, mutated somatically in adenomatous polyps and mutated in the germline of patients with familial adenomatous polyposis, is not linked to hereditary juvenile polyposis.
Adenomatous polyps of the appendix frequently had APC, KRAS and TP53 mutations and were morphologically and molecularly similar to adenomatous polyps of the colorectum.
Biallelic mutations for Y165C and/or G382D were not found in any of those undergoing screening colonoscopy with 0-3 polyps (n = 400), in those APC-negative patients with <20 adenomatous polyps (n = 26), or in those with CRC who were older than 50 years (n = 328).
Using real-time quantitative PCR, we demonstrated that several genes previously implicated in human colon cancer undergo altered expression in the APC(min) mouse adenomatous polyp, a precursor of cancer, as well as in normal-appearing surrounding mucosa.
The germ-line missense variant of the APC gene, E1317Q, has been proposed to confer a risk for colonic adenomatous polyps (adenomas), but not for CRCs in the general population.
Since some gastric cancers are considered to originate from the intestinal metaplasia, it is likely that the adenomatous polyposis coli (APC) gene, the mutation of which causes adenomatous polyps in the colon, is associated with carcinogenesis of gastric cancer.
Contribution of bi-allelic germline MUTYH mutations to early-onset and familial colorectal cancer and to low number of adenomatous polyps: case-series and literature review.
Adenomatous polyps of the appendix frequently had APC, KRAS and TP53 mutations and were morphologically and molecularly similar to adenomatous polyps of the colorectum.
Serum levels of the mutant p53 protein in patients with colorectal cancer (mean=0.97+/-0.14 ng/ml, ranged from 0.7 ng/ml to 1.37 ng/ml, n=50) were significantly greater than those in patients with adenomatous polyp (mean=0.73+/-0.06 ng/ml, ranged from 0.69 ng/ml to 0.83 ng/ml) (p<0.001).
Using Fisher's exact test and logistic regression, we compared the frequency of the known disease-causing MYH mutations Y165C, G382D and 466delE in 137 probands (117 cases with CRC and 20 cases diagnosed on the basis of adenomatous polyps only) from families with three or more CRCs but negative for mutations in the MMR genes and in 967 healthy controls with comparable ethnic backgrounds.
Lynch syndrome displays many curious features that cannot be accounted for by the prevailing concepts of carcinogenesis and genetics: (1) CRCs occur preferentially in the right side of the colon, whereas the majority of sporadic cases develop in the left colon; (2) the increased risk of CRC is not associated with an increased incidence of adenomatous polyps, which are necessary precancerous lesions in the development of common CRCs; (3) the tumor spectrum in Lynch syndrome is restricted to the colon and some extracolonic sites, whereas the responsible MMR genes are ubiquitously expressed; (4) the tumor risk, which is negligible during childhood, becomes significant during adulthood at the age of 25 and thereafter remains essentially constant throughout the ages.