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Oncotarget. 2017 Jun 28;8(37):62029-62038. doi: 10.18632/oncotarget.18790. eCollection 2017 Sep 22.

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

Oncotarget

Taigo Kato, Jae-Hyun Park, Kazuma Kiyotani, Yuji Ikeda, Yasuo Miyoshi, Yusuke Nakamura

Affiliations

  1. Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
  2. Divison of Breast and Endocrine, Department of Surgery, Hyogo College of Medicine, Hyogo 663-8501, Japan.
  3. Department of Surgery, The University of Chicago, Chicago, IL 60637, USA.

PMID: 28977923 PMCID: PMC5617483 DOI: 10.18632/oncotarget.18790

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

Keywords: T cell receptor; breast cancer; heterogeneity; neoantigen; non-synonymous mutation

Conflict of interest statement

CONFLICTS OF INTEREST We have no potential conflicts of interest related to this study.

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