Summary: This article discussed a substantial proportion of metastatic gastric cancers utilize alternate promoters as a mechanism of immune evasion, and these tumors may be resistant to anti-PD1 immune checkpoint inhibition. Alternate promoter utilization is thus a potential mechanism of resistance to immune checkpoint inhibition, and a novel predictive biomarker for immunotherapy.

Summary: Promoter elements play important roles in isoform and cell type–specific expression. In this article, the epigenomic promoter landscape of gastric adenocarcinoma, analyzing 110 chromatin profiles (H3K4me3, H3K4me1, H3K27ac) of primary gastric cancers, gastric cancer lines, and non-malignant gastric tissues were surveyed. About 2,000 promoter alterations (somatic promoters) were identified and deregulated in various epithelial malignancies which maps frequently to alternative promoters within the same gene. These epigenomic promoter alterations may thus drive intrinsic tumorigenesis and allow nascent cancers to evade host immunity.

Summary: Chromatin alterations are fundamental hallmarks of cancer. Chromatin alterations in primary gastric adenocarcinomas were studied using nanoscale Chromatin Immunoprecipitation Sequencing (nano ChIP-Seq) of multiple histone modifications in five gastric cancers and matched normal tissues. The article demonstrates the feasibility of profiling chromatin from solid tumours with limited tissue to identify regulatory elements, transcriptional patterns and regulatory genetic variants associated with cancer.

Summary: Regulatory enhancer elements in solid tumours remain poorly characterized. Micro-scale chromatin profiling was used to survey the distal enhancer landscape of primary gastric adenocarcinoma (GC), a leading cause of global cancer mortality. Integrating 110 epigenomic profiles from primary GCs, normal gastric tissues and cell lines, 36,973 predicted enhancers and 3,759 predicted super-enhancers respectively were highlighted. A genome-wide reprogramming of the GC enhancer and super-enhancer landscape during tumorigenesis was discovered, contributing to dysregulated local and regional cancer gene expression.

Summary: Gastric tumours with higher epigenetic promoter alterations exhibited decreased levels of T-cell cytolytic markers and expressed signatures of immune depletion. The article writes of an association between alternate promoter use and the tumour microenvironment, leading to immune evasion and immunotherapy resistance was demonstrated. Alternative promoter use burden may represent a predictive biomarker for immunotherapy applicable to multiple gastrointestinal tumour types.

Summary: In this review, the latest immune checkpoint inhibitor trials were described, which have been reported in gastroesophageal cancers with a focus on predictive biomarkers. Novel biomarkers being developed were explored to improve precision oncology for immunotherapy in gastroesophageal cancers.

Summary: Largest survey of promoter activity in human tissues and cancers (18,468 RNA-seq samples covering 42 cancer types), confirming known examples and identifying many alternative promoters that have not been associated with cancer. Article demonstrated the pervasive role of alternative promoters in context specific isoform expression and regulation of isoform diversity. Cancer-associated promoters alter the transcriptome independently from gene expression across different cancer types, and therefore Patient-to-patient variation in alternative promoters is associated with survival.

Summary: Gastric tumours with higher epigenetic promoter alterations exhibited decreased levels of T-cell cytolytic markers and expressed signatures of immune depletion. The article writes of an association between alternate promoter use and the tumour microenvironment, leading to immune evasion and immunotherapy resistance was demonstrated. Alternative promoter use burden may represent a predictive biomarker for immunotherapy applicable to multiple gastrointestinal tumour types.

Summary: In this review the latest immune checkpoint inhibitor trials were describeb, which have been reported in gastroesophageal cancers with a focus on predictive biomarkers. Novel biomarkers being developed were explored to improve precision oncology for immunotherapy in gastroesophageal cancers.

Summary: Largest survey of promoter activity in human tissues and cancers (18,468 RNA-seq samples covering 42 cancer types), confirming known examples and identifying many alternative promoters that have not been associated with cancer. Article demonstrated pervasive role of alternative promoters in context specific isoform expression and regulation of isoform diversity. Cancer-associated promoters alter the transcriptome independently from gene expression across different cancer types, and therefore Patient-to-patient variation in alternative promoter is associated with survival.