Deciphering molecular properties of hypermutated gastrointestinal cancer

Abstract

Great mutational heterogeneity is observed both across cancer types (>1000-fold) and within a given cancer type, with a fraction harboring >10 mutations per million bases, thus termed hypermutation. We determined the genome-wide effects of high mutation load on the transcriptome and methylome of two cancer types; namely, colorectal cancer (CRC) and stomach adenocarcinoma (STAD). Briefly, hierarchical clustering of the expression and methylation profiles showed that the majority of CRC and STAD hypermutated samples were mixed and separated from their respective non-hypermutated samples, exceeding the boundary of tissue specificity. Further in-detailed exploration uncovered that the underlying molecular mechanism may be related to the perturbation of chromatin remodeling genes.