Molecular subtypes in stage II-III colon cancer defined by genomic instability: early recurrence-risk associated with a high copy-number variation and loss of RUNX3 and CDKN2A.
Recently, we have shown anti-proliferative and pro-apoptotic effects of indicaxanthin associated with epigenetic modulation of the onco-suppressor p16INK4a in the human colon cancer cell line CACO2.
Having a CDKN2A mutation in the family increased the prevalence of other cancers (prevalence ratio [PR] 2.99, P=.012) and prevalence of pancreatic (PR 2.97, P=.006), lung (PR 3.04, P<.001), and breast (PR 2.19, P=.018) cancers but not nephrourologic or colon cancer.
In addition, an unfavorable prognosis (P < 0.05) was associated with low DLC1 and low p15(Ink4b) in lung cancer and colon cancer, low DLC1 and low p16(Ink4a) in lung cancer, low DLC1 and high CDK4 in lung cancer, and low DLC1 and high CDK6 in colon cancer.
Immunoprecipitation of nucleosomal DNA is a novel procedure to improve the sensitivity of serum screening for the p16 hypermethylation associated with colon cancer.
Aberrant methylation of p14ARF gene occurred more frequently in patients under 50 years of age and in left-sided colon cancers, and was not statistically significant.
Loss of MGMT protein expression was associated with the MSI-L phenotype but was not a prognostic factor for overall survival in colon cancer. p16 methylation was significantly less frequent in MSI-L than in MSI-H and MSS tumors and was not associated with survival.
The methylation level of CDKN2A was higher in cancer with the L-haplotype of MTHFR than in that with the H-haplotype when cancers of proximal origin were considered (p=0.029). hMLH1 methylation also tended to be higher in proximal colon cancers of MTHFR L-haplotype (p=0.059).
This highly polymorphic microsatellite marker (heterozygote frequency: 0.78) proved to be efficient for p16 allele loss and microsatellite instability analyses in human colon cancer.
The aim of this study was to evaluate p14ARF and p16INK4a gene inactivation and its association with some clinocopathological parameters in colon cancer.
Methylated p16 was found in 100% of colon cancer cell lines, 55% of colon cancers, 54% of adenomas, and 25% of transitional mucosa but not in normal colonic epithelium.
Recent evidence shows that transcriptional silencing as a consequence of hypermethylation of CpG islands is the predominant mechanism of p16INK4a gene inactivation in sporadic colon cancer.
We have investigated abnormal methylation of the 5' CpG islands of the p16/CDKN2 and p15INK4B genes as an alternative mechanism of inactivation of these genes in bladder and colon cancers.