High sensitivity scanning of colorectal tumors and matched plasma DNA for mutations in APC, TP53, K-RAS, and BRAF genes with a novel DHPLC fluorescence detection platform.
Mutations in the adenomatous polyposis coli (APC) gene are linked to the dysplastic transformation of colorectal polyps and represent an early step in the development of colorectal tumors.
Since the adenomatous polyposis coli (APC) gene is mutated in about 80% of sporadic colorectal tumors, and familial adenomatous polyposis is the consequence of a germline mutation of the same gene, we examined whether low alkaline sphingomyelinase activity is linked to APC gene mutations.
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.