Since Late-onset Alzheimer’s disease (LOAD) derives from a combination of genetic variants and environmental factors, epigenetic modifications have been predicted to play a role in the etiopathology of LOAD. Along with DNA methylation, histone modifications have been proposed as the main epigenetic modifications that contribute to the pathologic mechanisms of LOAD; however, little is known about how these mechanisms contribute to the disease’s onset or progression. In this review, we highlighted the main histone modifications and their functional role, including histone acetylation, histone methylation, and histone phosphorylation, as well as changes in such histone modifications that occur in the aging process and mainly in Alzheimer’s disease (AD). Furthermore, we pointed out the main epigenetic drugs tested for AD treatment, such as those based on histone deacetylase (HDAC) inhibitors. Finally, we remarked on the perspectives around the use of such epigenetics drugs for treating AD.

MYC and gastric adenocarcinoma carcinogenesis

Our study investigated the relationship between MYC alterations and clinicopathological features in gastric cancers. We evaluated the effect of MYC mRNA expression and its protein immunoreactivity, as well as copy number variation, promoter DNA methylation, and point mutations, in 125 gastric adenocarcinoma and 67 paried non-neoplastic tissues. We observed that 77% of the tumors presented MYC immunoreactivity which was significantly associated with increased mRNA expression (p<0.05). These observations were associated with deeper tumor extension and the presence of metastasis (p<0.05). MYC protein expression was also more frequently observed in intestinal-type than in diffuse-type tumors (p<0.001). Additionally, MYC mRNA and protein expression were significantly associated with its copy number (p<0.05). The gain of MYC copies was associated with late-onset, intestinal-type, advanced tumor stage, and the presence of distant metastasis (p<0.05). A hypomethylated MYC promoter was detected in 86.4% of tumor samples. MYC hypomethylation was associated with diffuse-type, advanced tumor stage, deeper tumor extension, and the presence of lymph node metastasis (p<0.05). Moreover, eighteen tumor samples presented at least one known mutation. The presence of MYC mutations was associated with diffuse-type tumor (p<0.001). Our results showed that MYC deregulation was mainly associated with poor prognostic features and also reinforced the presence of different pathways involved in intestinal-type and diffuse-type gastric carcinogenesis. Thus, our findings suggest that MYC may be a useful marker for clinical stratification and prognosis.

Cancer is considered one of the major health issues worldwide, and gastric cancer accounted for 8% of total cases and 10% of total deaths in 2008. Gastric cancer is considered an age-related disease, and the total number of newly diagnosed cases has been increasing as a result of the higher life expectancy. Therefore, the basic mechanisms underlying gastric tumorigenesis is worth investigation. This review provides an overview of the epigenetic mechanisms, such as DNA methylation, histone modifications, chromatin remodeling complex and miRNA, involved in gastric cancer. As the studies in gastric cancer continue, the mapping of an epigenome code is not far for this disease. In conclusion, an epigenetic therapy might appear in the not too distant future.

MYC deregulation is a common event in gastric carcinogenesis, usually as a consequence of gene amplification, chromosomal translocations, or posttranslational mechanisms. FBXW7 is a p53-controlled tumor-suppressor that plays a role in the regulation of cell cycle exit and reentry via MYC degradation.