In addition, p16 methylation in chronic gastritis lesions significantly correlated with H. pylori infection; however, such correlation was not observed in GC specimens.
The frequency of genomic alterations seen in SBA demonstrated distinct differences in comparison with either colorectal cancer (APC: 26.8% [85 of 317] vs 75.9% [4823 of 6353], P < .001; and CDKN2A: 14.5% [46 of 317] vs 2.6% [165 of 6353], P < .001) or gastric carcinoma (KRAS: 53.6% [170 of 317] vs 14.2% [126 of 889], P < .001; APC: 26.8% [85 of 317] vs 7.8% [69 of 889], P < .001; and SMAD4: 17.4% [55 of 317] vs 5.2% [46 of 889], P < .001).
Overall, 78% of GC cases harbored one clinically relevant GA or more, with the most frequent alterations being found in TP53 (50%), ARID1A (24%), KRAS (16%), CDH1 (15%), CDKN2A (14%), CCND1 (9.5%), ERBB2 (8.5%), PIK3CA (8.6%), MLL2 (6.9%), FGFR2 (6.0%), and MET (6.0%).
We aimed to evaluate the inactivation of COX-2, HMLH1 and CDKN2A by promoter methylation and its relationship with the infection by different Helicobacter pylori strains in gastric cancer.
The relatively high frequency of hypermethylation on p16 and the strong correlation between the immunoreactivity and methylation patterns suggest that methylation is an important mechanism for p16 gene inactivation in GC.
On the other hand, the observed pattern of p16 (INK4A) hypermethylation suggests that this event is a good marker for the gastric cancer pathway in the Pará state population.
In an effort to explore the underlying mechanism for the p16(INK4)-negative cases, a prospective study was also performed on 20 cases of gastric cancer to compare the level of the p16(INK4) protein with the methylation status of the p16(INK4) promoter.
The overexpression of p16 seems to be a common event in the development of both intestinal and diffuse type of gastric cancer and it is likely that it may be driven by features of the neoplastic state.
Furthermore, CDKN2 exon 1 or 2 genomic DNA from all the gastric-carcinoma tissues were PCR-amplified and sequenced and no genetic alteration was detected.
Thus, a marked decrease of p16 expression, caused by the aberrant methylation of the p16 gene promoter, is closely associated with the development of EBVaGC.
Relative expression of SNHG7 is upregulated in gastric cancer tissues and cells, and partially contributes to the development and progression of gastric cancer through regulation of p15 and p16 expressions.
However, defective mRNA transcription, sometimes by aberrant DNA methylation, might be one of the pathways of inactivation of the p16 gene that leads to the development of gastric carcinoma.
In nonneoplastic mucosa, p14, p16 and p73 methylation occurred in both EBV-associated (8/33, 6/34 and 3/38, respectively) and EBV-negative GC (6/23, 4/35, and 1/35). p73 methylation was observed in the mucosa without H. pylori infection in all 4 samples.
Our preliminary results indicate alterations in the p15 gene were not important in gastric tumorigenesis, while infrequent homozygous deletions in the p16 gene play a limited role in tumour progression of intestinal-type GC.