Intestinal metaplasia (IM) is a pre-cancerous condition, and connected with an increased risk of developing intestinal-type gastric adenocarcinoma, the most common form of gastric cancer (GC). However, only a small subset of IM patients develop GC. In a 10-year prospective study, Huang, Ramnarayanan, Zhu, Srivastava et al. performed (epi)genomic profiling of 138 IMs from 148 GC-free patients to determine molecular features, including Helicobacter pylori (Hp) status, associated with GC progression or IM regression. Compared with GCs, IMs had low frequencies of clonal mutations. IMs with somatic copy number alterations (sCNAs), telomere erosion and epigenomic alterations were associated with GC progression, indicating that epigenomic changes observed in a subset of IMs can be targeted to reduce GC progression. Finally, Hp-positive IMs were detected by sequencing at a higher rate than by histology, and were more likely to harbour sCNAs.
Huang, K. K. et al. Genomic and epigenomic profiling of high-risk intestinal metaplasia reveals molecular determinants of progression to gastric cancer. Cancer Cell 33, 137–150 (2018)