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.
Copyright © 2019 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use
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Carcinogenesis / genetics*
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Cell Cycle Proteins / antagonists & inhibitors
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Cell Cycle Proteins / genetics*
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Cell Line, Tumor
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Chromosomal Proteins, Non-Histone / antagonists & inhibitors
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Chromosomal Proteins, Non-Histone / genetics*
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Cohesins
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DNA Methylation
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DNA Repair / drug effects
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Epigenesis, Genetic
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Gene Expression Regulation, Neoplastic
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Genomic Instability
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Humans
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Mutation Rate
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Neoplasms / drug therapy
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Neoplasms / genetics*
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Nuclear Proteins / antagonists & inhibitors
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Nuclear Proteins / genetics*
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Promoter Regions, Genetic
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Synthetic Lethal Mutations / drug effects
Substances
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Antineoplastic Agents
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Cell Cycle Proteins
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Chromosomal Proteins, Non-Histone
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Nuclear Proteins
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STAG1 protein, human
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STAG2 protein, human