(selected excerpts below)Dear Editor,Alternative lengthening of telomeres (ALT) is a telomere maintenance mechanism (TMM) frequently observed in recalcitrant cancer. However, the TMM in the cancer stem-like subtype of gastric cancer (GC) is unknown. To assess the therapeutic targetability of the TMM, we analyzed transcriptome data of 497 GC patients,1 classified into ALT-like and non-ALT tumor groups based on chromatin decompaction. Among five GC subtypes (Figure 1A,C), 92.3% of stem-like subtype samples exhibited high-level chromatin decompaction. According to currently proposed ALT mechanisms, ZNF827 recruits the NuRD complex to telomeres. The resultant NuRD-ZNF827 complex has ALT-promoting activity....In this study, we demonstrate that ALT-like GC is associated with EMT, energy metabolic reprogramming, and mitochondrial biosynthesis. Additionally, we identified novel therapeutic targets specific to ALT-like tumors. Our study provides a new model of telomere extension and potential therapeutic strategies for the ALT-associated aggressive subtype of GC.