Whereas some patients showed a single epigenotype in all tumors throughout the colon, tumors with two distinct epigenotypes developed within a family with the same APC mutation or even within one patient.
Recent evidence suggests that the beta-catenin gene (CTNNB1) acts as an oncogene, and some human colon tumors with an intact APC gene have activating mutations in CTNNB1.
From this descriptive study, it seems that the short-term risk for colonic polyps in I1307KAPC mutation is low, primarily affecting patients with previously diagnosed colon tumors.
Using NGS, the following mutations were detected: nonsense mutations in four tumor suppressor genes [APCR1114X (molecular argument that the cancer was a primary tumor of colon), TP53 R213X, RB1 E137X and FBWX7 R393X & S282X], mutations in three receptor tyrosine kinases (RET A919V of high transforming activity, EGFR E114K and FLT3 L601I) well known as oncogenes.
The majority of colon tumors develop because of mutations in the tumor suppressor APC that lead to Wnt/beta-catenin signaling activation and subsequent transcription of target genes, including conductin/AXIN2.
We investigated the presence and patterns of mosaicism in the APC gene in patients with colon neoplasmsnot associated with any other genetic variants; we performed deep sequence analysis of APC in at least 2 adenomas or carcinomas per patient.
These results suggest the following mechanisms for the development of colon tumors in patients with familial adenomatous polyposis: (a) the heterozygous mutant/wild-type condition at the APC gene causes formation of mild or moderate adenoma; (b) the loss of the normal allele in the APC gene leads to a change from moderate to severe adenoma; (c) LOH on chromosome 17p contributes to the conversion of adenoma to intramucosal carcinoma; (d) LOH on other chromosomes, such as 18 and 22q, are involved in the progression of intramucosal carcinoma to invasive carcinoma; and (e) K-ras mutation may also affect the development of moderate to severe adenoma.
We determined the error spectrum of DNA polymerase beta in the human APC gene under PCR conditions and compared it with the set of mutations reported in human colon tumors.
To study the role of APC in signaling ODC expression, we used the human colon tumor cell line HT29 (wtAPC-/-), which has been stably transfected with a zinc-inducible wild-type APC gene.
Total meat consumption was not associated with the endpoints studied.Meat product (i.e. processed meat) consumption showed a positive association with colon tumours harbouring a truncating APC mutation, whereas beef consumption was associated with an increased risk of colon tumours without a truncating APC mutation (incidence rate ratio (RR) highest versus lowest quartile of intake 1.61, 95% confidence interval (CI) 0.96-2.71, p-trend = 0.04 and 1.58, 95% CI 1.10-2.25, p-trend = 0.01, respectively).
As most sporadic human colon tumors present adenomatous polyposis coli (APC) gene mutations, considerable effort has gone into developing mice that express mutant Apc alleles that mimic human colon cancer pathogenesis.
APC gene mutations have been associated to have a role in colon cancer and since gastric and colon tumors share some common genetic lesions, it is relevant to investigate the role of APC tumor suppressor gene in gastric cancer.
Our findings show that 150 ppm OSU-HDAC42 significantly inhibited small-intestinal polyps (>46%; P < 0.001), with polyp size measuring >1 mm (P < 0.001), and colon tumors (>26%) in APC(min/+)mice, whereas 300 ppm SAHA showed nonsignificant inhibition.
Accumulating mutations of p53 in colon tumor and hairy cell leukemia do not arise from methylation/deamination processes, but rather from nucleotide deletions and insertions.