Molecular alterations in gastric cancer and the surrounding intestinal metaplastic mucosa: an analysis of isolated glands

Background Intestinal metaplasias (IMs) are generally regarded as pre-neoplastic gastric lesions. However, molecular alterations including genetic and epigenetic changes occurring in individual IM glands are not well defined. Aims We sought to identify DNA methylation status, microsatellite instability (MSI) and allelic imbalance (AI) occurring in individual IM glands and non-IM glands within the same mucosa. Methods We divided examined isolated gland obtained from GC into 4 components: isolated cancer, antral isolated intestinal metaplastic tissue, antral isolated non-metaplastic gland and isolated non-metaplastic gland derived from the greater curvature of the most distant gastric body without mucosal atrophy. We examined AI and microsatellite instability statuses using PCR-based microsatellite analysis. Next, the DNA methylation status (high methylation epigenome [HME], intermediate methylation epigenome [IME], and low methylation epigenome [LME]) was investigated. DNA methylation analysis of CDKN2A, mir34-b/c and MLHI genes was also performed. Results Although antral isolated IM glands were characterized by IME, isolated non-IM glands showed LME. In isolated cancer glands, HME was frequently found, compared with isolated non-IM glands. DNA methylation of mir34-b/c was common in isolated cancer and IM glands, whereas DNA methylation of CDKN2A was a rare event in isolated samples. The MLH1 gene was not methylated in isolated non-IM glands. Although multiple AIs were frequently found in isolated cancer glands, a few AIs were detected in isolated IM glands. Conclusions We suggest that the DNA methylation status and the status of the mir34-b/c gene among isolated samples of IMs and isolated non-IM glands have an impact on IM development.