Genomic and immune profiling of pre-invasive lung adenocarcinoma

Nat Commun. 2019 Nov 29;10(1):5472. doi: 10.1038/s41467-019-13460-3.

Abstract

Adenocarcinoma in situ and minimally invasive adenocarcinoma are the pre-invasive forms of lung adenocarcinoma. The genomic and immune profiles of these lesions are poorly understood. Here we report exome and transcriptome sequencing of 98 lung adenocarcinoma precursor lesions and 99 invasive adenocarcinomas. We have identified EGFR, RBM10, BRAF, ERBB2, TP53, KRAS, MAP2K1 and MET as significantly mutated genes in the pre/minimally invasive group. Classes of genome alterations that increase in frequency during the progression to malignancy are revealed. These include mutations in TP53, arm-level copy number alterations, and HLA loss of heterozygosity. Immune infiltration is correlated with copy number alterations of chromosome arm 6p, suggesting a link between arm-level events and the tumor immune environment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma in Situ / genetics*
  • Adenocarcinoma in Situ / immunology
  • Adenocarcinoma in Situ / pathology
  • Adenocarcinoma of Lung / genetics*
  • Adenocarcinoma of Lung / immunology
  • Adenocarcinoma of Lung / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • DNA Copy Number Variations
  • ErbB Receptors / genetics
  • Female
  • Gene Expression Profiling
  • HLA Antigens / genetics
  • HLA Antigens / immunology
  • Humans
  • Loss of Heterozygosity
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / pathology
  • MAP Kinase Kinase 1 / genetics
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins c-met / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics
  • RNA-Binding Proteins / genetics
  • Receptor, ErbB-2 / genetics
  • Receptors, Antigen, B-Cell / genetics
  • Receptors, Antigen, T-Cell / genetics
  • Tumor Suppressor Protein p53 / genetics
  • Whole Exome Sequencing

Substances

  • HLA Antigens
  • KRAS protein, human
  • RBM10 protein, human
  • RNA-Binding Proteins
  • Receptors, Antigen, B-Cell
  • Receptors, Antigen, T-Cell
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • EGFR protein, human
  • ERBB2 protein, human
  • ErbB Receptors
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • Receptor, ErbB-2
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • MAP Kinase Kinase 1
  • MAP2K1 protein, human
  • Proto-Oncogene Proteins p21(ras)