STAG Mutations in Cancer

Trends Cancer. 2019 Aug;5(8):506-520. doi: 10.1016/j.trecan.2019.07.001. Epub 2019 Jul 31.

Abstract

Stromal Antigen 1 and 2 (STAG1/2) are key subunits of the cohesin complex that mediate sister chromatid cohesion, DNA repair, transcriptional regulation, and genome topology. Genetic alterations comprising any of the 11 cohesin-associated genes possibly occur in up to 26% of patients included in The Cancer Genome Atlas (TCGA) studies. STAG2 shows the highest number of putative driver truncating mutations. We provide a comprehensive review of the function of STAG1/2 in human physiology and disease and an integrative analysis of available omics data on STAG alterations in a wide array of cancers, comprising 53 691 patients and 1067 cell lines. Lastly, we discuss opportunities for therapeutic intervention.

Keywords: STAG1; STAG2; cancer; chromosomal instability; cohesin; genome organization.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Carcinogenesis / genetics*
  • Cell Cycle Proteins / antagonists & inhibitors
  • Cell Cycle Proteins / genetics*
  • Cell Line, Tumor
  • Chromosomal Proteins, Non-Histone / antagonists & inhibitors
  • Chromosomal Proteins, Non-Histone / genetics*
  • Cohesins
  • DNA Methylation
  • DNA Repair / drug effects
  • Epigenesis, Genetic
  • Gene Expression Regulation, Neoplastic
  • Genomic Instability
  • Humans
  • Mutation Rate
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / genetics*
  • Promoter Regions, Genetic
  • Synthetic Lethal Mutations / drug effects

Substances

  • Antineoplastic Agents
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Nuclear Proteins
  • STAG1 protein, human
  • STAG2 protein, human