We have added the APC germline-mutation data for Taiwanese FAP patients and indicated the presence of an FAP subgroup comprising affected individuals with nonadenomatous polyps or less than 100 adenomatous polyps; this form of FAP is less frequently caused by germline mutations of the APC gene.
Mutations in APC causing Gardner's syndrome are clustered in a region encoding a series of amino-acid repeats responsible for the binding to beta-catenin.
Assessment of APC promoter methylation revealed that normal tissues were unmethylated, while twenty out of forty five (44.4%) tumor tissues were hypermethylated either in one or both alleles of APC.
In truncated APC, the CID is absolutely necessary to down-regulate the transcriptional activity and the level of beta-catenin, even when an axin/conductin binding site is present.
These results indicated that the LOH of APC and p53 mutation has already occurred by the Dukes' A lake 'suppressor pathway' but not the KRAS mutation in MSI-L CRCs.
In this study we set out to test the hypothesis that loss of Rassf1a can cooperate with inactivation of the adenomatous polyposis coli (Apc) gene to accelerate intestinal tumourigenesis using the Apc-Min (Apc(Min/+)) mouse model, as mutational or deletional inactivation of APC is a frequent early event in the genesis of intestinal cancer.
Because dynactin, a dynein regulator, interacts with end-binding protein 1 (EB1) and beta-catenin, two known binding partners of the adenomatous polyposis coli (APC) protein, we looked for a genetic interaction between Lis1 and APC.
In our study, we used bisulfite treatment and direct sequencing of 2 regulatory regions of APC containing a total of 25 CpG dinucleotides, to investigate the possible role of germline hypermethylation of the APC promoter in FAP and AFAP families that were negative forAPC and MUTYH mutations.
CTNNB1 and APC are part of the Wnt signaling pathway and mutations in either gene result in stabilization of the beta-catenin protein and allow nuclear translocation and binding of beta-catenin to the T-cell factor/lymphoid enhancer factor (TCF/Lef) family of transcription factors, resulting in activation of target genes which may underlie desmoid tumor biology and clinical behavior.
In our study, we used bisulfite treatment and direct sequencing of 2 regulatory regions of APC containing a total of 25 CpG dinucleotides, to investigate the possible role of germline hypermethylation of the APC promoter in FAP and AFAP families that were negative forAPC and MUTYH mutations.
Most APC gene mutations cause deletion of the C terminus and disrupt APC regulation of beta-catenin turnover, microtubule dynamics, and chromosome segregation.
Because dynactin, a dynein regulator, interacts with end-binding protein 1 (EB1) and beta-catenin, two known binding partners of the adenomatous polyposis coli (APC) protein, we looked for a genetic interaction between Lis1 and APC.
Most cases of colorectal cancer are initiated by hyperactivation of the Wnt/beta-catenin pathway due to mutations in the APC tumour suppressor, or in beta-catenin itself.
Promoter hypermethylation was observed in 25/50 (50%) IDCs for CDH1 and in 11/50 (22%) tumors for APC, associated with loss of expression of E-CD and APC proteins; concordant hypermethylation of these genes was observed in paired patients' sera.
We identified the APCN1026S variant of unknown malignant potential in the adenomatous polyposis coli (APC) gene in a Spanish attenuated familial adenomatous polyposis (AFAP) family.
There was no relationship of hypermethylation of any gene, including MGMT, with G-to-A or C-to-T transitions in KRAS or P53, although APC hypermethylation was associated with P53 mutation (P < 0.0002).
APC has both nuclear localization signals and nuclear export signals in its molecule, suggesting its occasional nuclear localization and export of beta-catenin from the nucleus.