APC mosaicism was assumed if the same loss-of-function APC mutation was present in ≥ 2 anatomically separated colorectal adenomas/carcinomas per patient.
We screened for germ-line MYH mutations in 152 patients with multiple (3 to 100) colorectal adenomas and 107 APC-mutation-negative probands with classic familial adenomatous polyposis (>100 adenomas).
Adenomatous polyposis coli (Apc) gene mutations commonly occur in human colorectal adenomas and carcinomas, leading to Wnt signalling pathway activation.
Somatic mutations of APC are also observed in about 60% of sporadic colorectal adenomas and carcinomas, suggesting that disruption of this putative tumor suppressor gene may play a role in both familial as well as acquired colorectal tumorigenesis.
These results indicated that MYH-associated polyposis (MAP) is present in about 20% of Italian FAP/AAPC patients, in whom no germline APC mutation is detectable and showing a family history compatible with recessive inheritance, and in a small fraction of patients with colorectal adenomas in the general population.
Finally, E2F4 was found to be overexpressed, phosphorylated and nuclear localized in epithelial cells from human colorectal adenomas exhibiting mutations in APC and KRAS or BRAF genes, known to deregulate GSK3/β-catenin and MEK/ERK signaling, respectively.
The promoter methylation status of 4 tumor-related genes (RARB2, p16INK4a, MGMT, and APC) was analyzed in DNA stool samples and corresponding tissues in an initial set of 12 patients with newly diagnosed primary colorectal carcinomas and 20 patients with newly diagnosed colorectal adenomas, using methylation-specific polymerase chain reaction.
Inherited mutations in MYH predispose to colorectal adenomas and carcinomas that show a characteristic pattern of somatic G:C-->T:A mutations in the APC gene.
The frequency of APC promoter hypermethylation was significantly higher in colorectal adenoma than in normal colorectal tissue, OR was 5.76, 95% CI, 2.45-13.56; p<0.0001, I2=0%.
We have screened 164 unrelated patients with 'multiple' (3-100) colorectal adenomas for germline variants throughout the APC gene, including promoter mutations.
APC is a critical component of the Wnt/Wingless signaling pathway, which is disrupted in sporadic cancers (e.g., colorectal adenomas, hepatocellular carcinomas, and medulloblastomas) by somatic mutations affecting multiple genes encoding alternative pathway components, including APC and CTNNB1 (encoding beta-catenin).
The adenomatous polyposis coli (APC) gene is a tumor-suppressor gene involved in familial polyposis coli (FAP), a hereditary disease heralded by the development of hundreds of colorectal adenomas.
In this study, mutation analysis of the adenomatous polyposis coli (APC) gene using the protein truncation test (PTT) in 20 flat colorectal adenomas in a selected group of 16 patients without hereditary predisposition to colorectal cancer, revealed double truncations of the APC gene in four adenomas.
To study the types of APC gene mutations and their relation to clinicopathological features which are associated with malignant potential, the mutation cluster region of the APC gene was analysed in a series of 32 human sporadic colorectal adenomas from 22 patients.
Given the significance of APC in colorectal cancer, we investigated the association between common single-nucleotide polymorphisms (SNP) in the APC gene and the odds of developing metachronous colorectal adenomas as a surrogate measure of colorectal cancer risk.