Nanoscale Chromatin Profiling of Gastric Adenocarcinoma

To identify chromatin alterations in primary gastric adenocarcionomas, we performed nano-scale chromatin immunoprecipitation-sequencing (Nano-CHiPseq) of histone modifications in 5 gastric cancers and matched normal tissues, We identified hundreds of somatically-altered promoters (marked by H3K4me3) and enhancers (H3K4me1). The majority of cancer-associated promoters localized to genomic sites lacking previously-annotated transcription start sites (“cryptic promoters”), driving high expression of nearby genes implicated in gastrointestinal cancers, embryonic development, and tissue specification. Our findings demonstrate the feasibility of performing chromatin profiling on solid tumors where tissue is limiting, to identify in non-coding regions regulatory elements, transcriptional patterns and genetic variants associated with cancer. We propose a pervasive role for cryptic promoters in the reactivation of early developmental programs in gastric cancer, and the potential utility of cryptic promoters as biomarkers of malignancy. Overall design: Five gastric cancer tumor normal pairs are profiling in multiple number of chromatin marks