Integrated analysis of somatic mutations and immune microenvironment of multiple regions in breast cancers.

ABSTRACT: Next-generation sequencing technology enables us to analyze the complexity of intra- and inter-tumoral heterogeneity, which may influence to prognosis of cancer patients. In this study, we collected surgically-resected tumor tissues from five breast cancer patients and characterized three different portions of individual tumors through somatic mutation analysis by whole exome sequencing, T cell receptor beta (TCRB) repertoire analysis of tumor-infiltrating lymphocytes (TILs), and the expression analysis of immune-related genes at 15 different sites. This integrated analysis revealed distinguished patterns of somatic mutations and TIL clonotypes in the three portions of each tumor, implying that the tumor heterogeneity is comprised by spatially different somatic mutations as well as the presence of diverse T cell clones. Furthermore, higher numbers of the non-synonymous somatic mutations were significantly correlated with the higher ratio of GZMA/TCRB expression (P = 0.0004), implying that high somatic mutation load in tumor might be correlated to the number of immunogenic antigens and then functionally activate TILs with higher cytolytic activity. Our findings suggest that breast cancers comprise with very complex tumor heterogeneity by the spatially different mutational landscape and immune microenvironment, and that mutation/neoantigen load may be strongly correlated with induction of cancer-specific TILs and affect the immune microenvironment in breast tumors.

SUBMITTER: Kato T 

PROVIDER: S-EPMC5617483 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature