We screened the entire coding region of APC and also assessed 5q LOH, 5q MSI, and promoter hypermethylation in fresh colorectal tissue and the lymphocytes of 31 patients with synchronous colorectal adenoma and carcinoma.
We have studied this hypothesis by sequencing the adenomatous polyposis coli (APC) gene in 691 unrelated North American patients with CRAs and 969 matched healthy controls.
Molecular changes (K-ras and beta-catenin mutations, chromosome 18q allele loss (LOH), APC LOH, microsatellite instability (MSI), and expression of beta-catenin and p53) were examined in four series of CRC patients with proven or probable hereditary disease: hereditary non-polyposis colon cancer (HNPCC); MYH associated polyposis (MAP); multiple (>5) colorectal adenomas without familial adenomatous polyposis (FAP); and other families/cases referred to family cancer clinics (FCC series).
We studied 26 unrelated patients (and 16 relatives) with multiple colorectal adenomas (3-100, by endoscopic analysis) that had screened APC mutation-negative by protein truncation test.
Patients with familial APC (FAP) carry germ-line mutations in the APC gene and develop multiple colorectal adenomas and subsequent carcinomas early in life.
To determine the prevalence of pathogenic APC and MUTYH mutations in patients with multiple colorectal adenomas who had undergone genetic testing and to compare the prevalence and clinical characteristics of APC and MUTYH mutation carriers.
Therefore, we studied expression of DP1 and DP2 receptors by reverse transcription-polymerase chain reaction analysis of receptor mRNA levels in five human colorectal cancer cell lines (HT-29, HCA-7, HCT116, SW480 and SW48) and VACO-235 human colorectal adenoma cells.
beta-Catenin is essential for the function of cadherins, a family of Ca2+-dependent cell-cell adhesion molecules, by linking them to (alpha)-catenin and the actin cytoskeleton. beta-Catenin also binds to adenomatous polyposis coli (APC) protein, a cytosolic protein that is the product of a tumor suppressor gene mutated in colorectal adenomas.
Familial adenomatous polyposis (FAP) is a dominantly inherited syndrome caused by germline mutations in the APC gene and characterized by the development of multiple colorectal adenomas and a high risk of developing colorectal cancer (CRC).
Biallelic germ-line variants of the 8-hydroxyguanine repair gene MYH have been associated with multiple colorectal adenomas that display somatic G:C-->T:A transversions in APC.
Germline mutations in the adenomatous polyposis coli (APC) gene are responsible for familial adenomatous polyposis (FAP), an autosomal dominant hereditary predisposition to the development of multiple colorectal adenomas and of a broad spectrum of extra-intestinal tumors.
Four hundred fifty-three APC-negative patients with more than five colorectal adenomas were screened for mutations on the entire coding sequence of the MYH gene.
GSEA demonstrated a strong association between duodenal adenoma/adenocarcinomas with colorectal adenomas (p < 10<sup>-5</sup>) and gene expression patterns seen after APC gene knockout (p < 10<sup>-5</sup>), suggesting that the Wnt/β-catenin pathway plays a crucial role in the carcinogenesis of these neoplasms.
However, recent studies revealed that inactivation of the APC gene also plays a significant role in development of sporadic forms of colorectal adenoma and carcinoma.
Recently, biallelic germ-line mutations of MUTYH have been found in patients predisposed to a recessive form of hereditary multiple colorectal adenoma and carcinoma with an increased incidence of G:C to T:A somatic mutations in the APC gene.
Familial adenomatous polyposis (FAP) is characterised by the development of hundreds to thousands of colorectal adenomas and results from inherited or somatic mosaic variants in the APC gene.
There is increasing evidence that there exist germ-line variants of the APC gene that predispose to the development of multiple colorectal adenomas and carcinoma, but without the florid phenotype of classical FAP, and possibly with importance for colorectal cancer risk in the general population.