Somatic APC mutations in colorectal tumors with an RER phenotype reflect excessive frameshift mutations, especially in simple repetition tracts within the coding sequence.
Our results support the hypothesis that <i>APC</i>-mutant colorectal tumors are transcriptionally distinct from <i>APC</i>-wild-type colorectal tumors with canonical WNT signaling activated by other mechanisms, with possible implications for stratification and prognosis.<b>Significance:</b> These findings suggest that colon adenomas driven by APC mutations are distinct from those driven by WNT gain-of-function mutations, with implications for identifying at-risk patients with advanced disease based on gene expression patterns.<i></i>.
Analysis of colorectal tumors identified somatic APC mutations in the cluster region in all polyps, but no loss of heterozygosity was detected in any polyp.
Since the alteration of the APC gene occurs early in most colorectal tumors, the detection of APC mutations in fecal tumor DNA by HD-PCR may be a powerful tool in non-invasive cancer diagnostics.
The mutations in the adenomatous polyposis coli (APC) gene that initiate colorectal tumors theoretically provide an optimal marker for detecting colorectal tumors.
Alterations of phosphorylation sites within the CTNNB1 gene, which codes for beta-catenin has been reported to occur in about one-half of colorectal tumors without APC-gene mutations.
Turcot syndrome is clinically characterized by the occurrence of primary brain tumor and colorectal tumor and has, in previous reports, been shown associated with germline mutations in the genes APC, MLH1, MHS6, and PMS2.
Germ-line mutations in the tumor suppressor gene APC are associated with hereditary familial adenomatous polyposis (FAP), and somatic mutations are common in sporadic colorectal tumors.
Although mutation of the APC gene is an integral component of sporadic colorectal carcinogenesis, alteration in the region including the MOM gene does not appear to play a significant role in the development or clinicopathologic behavior of human sporadic colorectal tumors.
Thus, in both upper gastrointestinal and colorectal tumors, a specific region of the APC gene is associated with severe disease, clustering of somatic mutations, and loss of the wild-type allele.
These findings support a model where somatic instability of the (A)8 tract produced by the APC I1307K allele leads to increased APC gene inactivation and directly accounts for 42% of the colorectal neoplasms occurring in APC I1307K carriers.
Turcot's syndrome is characterized clinically by the occurrence of primary brain tumor and colorectal tumor and has in previous reports been shown to be associated with germline mutations in the genes APC, hMLH1, and hPMS2.
Moreover, APC promoter hypermethylation is observed in approximately 20% of sporadic colorectal tumors and correlates with the loss of gene expression.
APC mutations are generally sufficient for colorectal tumors to grow to about 1-cm diameter, although chance mutations at other loci can provide these early colorectal adenomas with a selective advantage, and some colorectal tumors may develop along a pathway not involving APC.
Recently, however, a missense variant of APC (I1307K) was described that confers an increased risk of colorectal tumors, including multiple adenomas, in Ashkenazim.
Germline mutations of the APC gene are responsible for familial adenomatous polyposis, an autosomal dominant inherited predisposition to colorectal tumors.
Finally, sequencing and fluorescence in situ hybridization analysis of the gene APC underlined that a somatic UPD event might represent the second hit to achieve biallelic inactivation of this TSG in colorectal tumors.