Disease relevance of Genes, APC

• Familial adenomatous polyposis is an autosomal dominant disease caused by a germ-line mutation of the adenomatous polyposis coli (APC) gene that causes colorectal cancer if prophylactic colectomy is not performed [1].
• Most inherited mutant alleles of the adenomatosis polyposis coli gene (APC) cause the appearance of large numbers of colon polyps, the familial polyposis syndrome [2].
• The adenomatous polyposis coli gene (APC) is mutated in most colon cancers [3].
• Familial adenomatous polyposis (FAP) is caused by mutations in the adenomatous polyposis coli (APC) gene, and different mutations may produce different clinical pictures [4].
• However, when combined with a mutation in the adenomatous polyposis coli (Apc) gene, double heterozygous animals have increased numbers of adenocarcinomas and decreased survival [5].

High impact information on Genes, APC

• The adenomatous polyposis coli gene (APC) is a major controller of the Wnt pathway and is essential to prevent tumorigenesis in a variety of tissues and organs [6].
• A human Dlg homolog, hDlg, has been implicated in tumorigenic processes via its association with the product of the Adenomatous Polyposis Coli (APC) gene [7].
• BACKGROUND & AIMS: Infantile and childhood liver tumors have been found in 0.42% of individuals with a germline mutation in the adenomatous polyposis coli (APC) gene [8].
• In contrast, allelic losses of 5q (adenomatous polyposis coli [APC] gene region) and 18q (deleted in colorectal cancer [DCC] gene region) were rare [9].
• We searched for somatic mutations of the adenomatous polyposis coli (APC) gene in DNA samples isolated from 57 sporadic gastric cancers, by means of a ribonuclease (RNase) protection analysis coupled with DNA amplification by the polymerase chain reaction (PCR) [10].

Biological context of Genes, APC

• Recently, a germline missense mutation, I1307K, was identified in the adenomatous polyposis coli (APC) gene that was suggested to increase cancer predisposition in Ashkenazi Jews [11].
• Dinucleotide repeat polymorphism at the D5S134 locus linked to the adenomatous polyposis coli (APC) gene [12].
• We have found a significant concordance between the in vitro replication errors of human DNA polymerase beta and in vivo point mutations of the adenomatous polyposis coli (APC) gene that leads to colon cancer [13].
• The heterozygote Min/+ mouse model, like patients with familial adenomatous polyposis, carries a nonsense mutation in the adenomatous polyposis coli (APC) gene that results in the spontaneous development of intestinal adenomas (100% incidence) [14].
• About 80% of the mutations identified to date in the Adenomatous Polyposis Coli (APC) gene have been found in the 5' half of the coding sequence, the vast majority of which (>95%) are nonsense or frameshift mutations that result in the loss of the carboxyl terminus of APC protein [15].

Anatomical context of Genes, APC

• Here, we directly test this association by using a Cre-LoxP strategy to inactivate the Adenomatous Polyposis Coli (Apc) gene in the murine renal epithelium [16].
• Papillary thyroid carcinoma (PTC) is a rare extracolonic manifestation of familial adenomatous polyposis, determined by germline mutations of the adenomatous polyposis coli (APC) gene [17].
• Damage to the human adenomatous polyposis coli (APC) gene is responsible for not only familial adenomatous polyposis but also many sporadic cancers of the entire digestive tract [18].
• Furthermore, loss of apc gene function probably induces COX-2 mRNA in gastrointestinal mucosa [19].
• The earliest event being the inactivation of both alleles of the Adenomatous Polyposis Coli (APC) gene, it is thought that the stem cells are the most likely target for these two first hits [20].

Associations of Genes, APC with chemical compounds

• Treatment of female C57BL/6J (B6) mice carrying the mutant Min allele of the adenomatous polyposis coli (Apc) gene with ethylnitrosourea (ENU) results in approximately 90% of mice developing an average of three mammary tumors within 65 days [21].
• Activation of adenomatous polyposis coli (APC) gene expression by the DNA-alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine requires p53 [22].
• However, glucose repression of APC genes was Mig1p and Mig2p independent, indicating the presence of an uncharacterized factor [23].
• Furthermore, Mig1p and Mig2p activate APC gene transcription, particularly on glycerol, and mig2Delta, but not mig1Delta, confers a prolonged replicative life span in both APC5 and acp5CA cells [23].
• Four of eight tumors had a total of five mutations in the Apc gene, four of which featured a guanine deletion from 5'-GTGGGAT-3' sequences [24].

Gene context of Genes, APC

• Mutations in the Adenomatous Polyposis Coli (APC) gene up-regulate Wnt signaling by stabilizing beta-catenin and causing activation of targets important in proliferation control [25].
• The beta-catenin and the adenomatous polyposis coli (APC) genes were analyzed for gene mutations [26].
• The normally lethal deletions of APC genes were suppressed by the double deletion of the PDS1 and CLB5 genes in conjunction with the insertion of multiple copies of the SIC1 gene controlled by its endogenous promoter [27].
• BACKGROUND & AIMS: Inactivation of the adenomatous polyposis coli (APC) gene is observed at early stages of intestinal tumor formation, whereas loss of E-cadherin is usually associated with tumor progression [28].
• LOH was assessed using a panel of 9 polymorphic markers for evaluation of the P53 gene on 17p, P16 on 9p, DCC and SMAD4 on 18q and the APC gene on 5q [29].

Analytical, diagnostic and therapeutic context of Genes, APC

• Reverse transcription-PCR combined with either (a) restriction enzyme digestion and repeat PCR or (b) ligase chain reaction has identified two new alternatively spliced transcripts of the adenomatous polyposis coli (APC) gene [30].
• Expression of the adenomatous polyposis coli (APC) gene derived exon BS (e.g., brain-specific exon) has been analyzed by RT-PCR [31].
• Detection of sequence variations in the adenomatous polyposis coli (APC) gene using denaturing high-performance liquid chromatography [32].
• Evidence linking COX-2 activity to carcinogenesis was derived from epidemiologic studies and animal models with defect adenomatous polyposis coli (APC) gene [33].

References