The adenomatous polyposis coli (APC) gene is mutated within specific sequence contexts in colorectal carcinomas but the underlying mechanism is not fully understood.
To further investigate the role of Wntless in tumorigenesis, APC-deficient spontaneous intestinal tumors and chemical induced colorectal cancer mouse models were employed.
We studied thirteen single nucleotide polymorphisms (SNPs) located in SFRP3 (rs7775), CTNNB1 (β-catenin) [rs4135385, rs13072632], APC (rs454886, rs459552), LRP6 (rs2075241, rs2284396), DKK4 (rs3763511), DKK3 (rs6485350), TCF4 (rs12255372) and AXIN2 (rs3923086, rs3923087, rs4791171) in patients with colorectal cancer (n = 122) and controls (n = 110).
Mutations in the adenomatous polyposis coli (APC) gene initiate the majority of both sporadic and hereditary colorectal cancers (CRC) and around 30% of these mutations are nonsense mutations.
IMPLICATIONS: The tumor-suppressive function of APC, the most frequently mutated gene in colorectal cancer, is mainly attributed to its role in β-catenin/Wnt signaling.
To obtain new insights into the mechanisms underlying APC mutation and to elucidate the mechanisms of CRC development, we performed to identify the potential metabolites in FAP based on metabolomic strategy.
Colorectal cancer (CRC) development is characterized by the stepwise accumulation of mutations over time, of which mutations in the tumor suppressor APC are often very early to occur.
The remaining case was CIMP negative and MMR proficient in both the components, harbored a BRAF mutation in the SSA/P counterpart, whereas the CRC one was APC and TP53 mutated and showed p16 and β-catenin dysregulation.
Colorectal cancers (CRCs) initiate through distinct mutations, including in APC pathway components leading to tubular adenomas (TAs); in BRAF, with epigenetic silencing of CDX2, leading to serrated adenomas (SAs); and in the DNA mismatch repair machinery driving microsatellite instability (MSI).
Inactivation of the Adenomatous polyposis coli (APC) gene is an initiating and the most relevant event in most sporadic cases of colorectal cancer, providing a rationale for using Apc-mutant mice as the disease model.
Although the genetic spectrum of human colorectal cancer (CRC) is mainly characterized by APC, KRAS and TP53 mutations, driver genes in tumor initiation have not been conclusively demonstrated.
The adenomatous polyposis coli (APC) gene plays a pivotal role in the pathogenesis of colorectal carcinoma (CRC) but remains a challenge for drug development.
Two familial forms of colorectal cancer (CRC), Lynch syndrome (LS) and familial adenomatous polyposis (FAP), are caused by rare mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2) and the genes APC and MUTYH, respectively.
While not all APC mutant peptides are inmmunogenic, a few qualify as vaccine candidates offering novel treatment opportunities to patients with somatic APC gene mutations to delay/treat colorectal cancer.