Molecular heterogeneity of gastric cancer explained by methylation-driven key regulators.

Abstract

Abstract Gastric cancer (GC) is a heterogeneous disease in which diverse genetic, genomic, and epigenetic alterations can accumulate in different molecular and histologic subtypes. Tumor microenvironment (TME) also contributes to the heterogeneity of GC. To investigate what molecular features of tumor cells drive GC heterogeneity, we developed an integrative causal model, called Integrative Sequential Causality Test (ISCT), to identify key regulators of GC by integrating DNA methylation, copy number variation, and transcriptomic data. Applying ISCT to three GC cohorts that contain methylation, CNV, and gene expression data, 11 common methylation-driven key regulators were iden..