Exome Sequencing Analysis Of Intestinal Metaplastic Tissue In Precancerous Lesions

Gastric cancer is the most prevalent cancer with high incidence rate,extremely,mortality rate is the third leading cause of death from cancer.It occurred in approximately 950000 people approximately 700000 died of the disease annually worldwide.At present,the patients clinically diagnosed are often at an advanced stage of gastric cancer,even metastasis,which is a huge problem.Therefore,the exhaustive study of gastric cancer in early stage is the key to diagnosis,thus sharply reducing the mortality of gastric cancer is way to go.Gastric cancer of intestinal type has a clear process of early lesions with varying degrees of adenoid differentiation characteristics.Intestinal gastric cancer starts with the infecton Helicobacter pylori(H.pylori,Hp)to normal gastric epithelial cells,developed through a series of procedures from inflammation to intestinal metaplasia,then dysplasia,and finally cancer.Intestinal metaplasia is deemed to be the point of no return in this series of precancerous lesions.Previously,large-scale epidemiological studies have shown that the presence of intestinal metaplasia can increase the risk of gastric cancer up to 6 times,but the mechanism by which intestinal metaplasia increases the risk of gastric cancer remains unclear.Our previous studies have shown that intestinal metaplasia microsatellite instability occurred in IM,indicating that gene mismatch repair system has been broken.In this paper,we analyzed the genomic characteristics of intestinal metaplasia from the perspective of total exon,and studied the molecular basis of malignant transformation of intestinal metaplasia.In this study,we used exome high-throughput sequencing to study a series of changes and mutations in the intestinal metaplasia gland,then a statistical study of the association between intestinal metaplasia and gastric cancer was carried out.Through exon sequencing,we found that genomic instability was common in the early stage of gastric cancer.Moreover,the mutation spectrum and context were similar in control and intestinal metaplasia.But IM genome shows considerable genomic instability in exonic regions compared with the control sample.Astonishingly,IM genome mutation patterns were similar to those in gastric cancer(TCGA data).MUC family,which protected the epithelial cells from the malignant environment,is a somatic mutation where protein is changed,The specific faction need more data.Very few gastric cancer drivers – might be one of the reasons why not fully malignant,which would occur after mutations accumulated to a certain extent and under the stimulation of the appropriate microenvironment.In conclusion,through exon sequencing,this study shows that there has high frequency genomic instability in precancerous lesions of intestinal metaplasia.Which has excessive clinical significance and can conduct the early detection of cancer,reduce gastric cancer mortality.